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Mycobacterium tuberculosis enters the body through the respiratory tract, produces and releases virulence proteins through a variety of mechanisms, regulates the host immune mechanism through a variety of ways, and then survives in the body for a long time. These depend on virulence genes encoded by Mycobacterium tuberculosis. Previous studies found that the Rv3435c gene of Mycobacterium tuberculosis is highly conserved in pathogenic mycobacterium, but not conserved in non-pathogenic mycobacterium, which may be a potential virulence gene, and inhibit the secretion of inflammatory factors in RAW264.7 cells and inhibit cell apoptosis. Based on previous studies, the function ofRv3435c gene in mice was studied by infecting mice with recombinant strains. In vivo infection experiments showed that overexpression of Rv3435c significantly promoted the survival of Ms in the lung. Ms-pMV361-Rv3435c specifically inhibits the secretion of inflammatory cytokines, including TNF-α, IL-6, IL-1β, IL-12, and IFN-γ.Rv3435c can inhibit lung cell apoptosis and cause pathological damage to lung. Therefore, Rv3435c enhances the survival of mycobacterium in mice and promotes the pathogenicity and spread of Mycobacterium tuberculosis by inhibiting the production of cytokines., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The exponential use of plastics and their recalcitrant nature leads to their significant accumulation in the environment. The occurrence of plastic wastes is considered as a serious environmental problem. Additionally, plastic wastes can break down into smaller pieces called microplastics (MPs), leading to further interactions with the environment and living organisms. In this study, sixty-six strains were isolated from microplastic particles collected on different coastal areas of Monastir and Mahdia (Tunisia). The different bacterial isolates were identified according to some biochemical tests such as catalase, oxidase, and were subjected to molecular characterization. Amplification of the internal transcribed spacer (ITS) revealed the presence of 31 ITS haplotypes. The partial sequencing of the 16S ribosomal DNA of representative strains was analyzed. The majority of bacterial isolates (84.31 %) belonged to Gamma-proteobacteria (84.78 %), while the remaining isolates were affiliated to Firmicutes (15.21 %). The microplastic-associated bacterial isolates belonged to 10 genera, namely Acinetobacter, Pseudomonas, Bacillus, Staphylococcus, Shewanella, Aeromonas, Vibrio, Stutzerimonas, Exiguobacterium, Enterobacter. Among the well-represented Acinetobacter genus, the most common species identified was Acinetobacter johnsonii. Susceptibility patterns of these strains were studied against 21 antibiotics commonly used in Tunisia. A high level of antibiotic resistance was observed for Penicillin G (97.82 %) and Temocillin (86.95 %). S26 strain presented the highest multidrug resistance with a multiple antibiotic resistance (MAR) index of 0.71., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Leptospirosis is major zoonotic disease with global implications, affecting both domestic animals and humans. It is caused by Leptospira interrogans (L. interrogans), which can damage multiple organs, including the kidneys, liver, testes, and uterus. Despite this, L. interrogans can also persist asymptomatically in tissues, akin to nonpathogenic strains. The mechanisms driving asymptomatic infections remain poorly understood. This study investigated the role of L. interrogans in asymptomatic infection within the uterine tissue of canines, focusing on the differential expression of Toll-like receptors (TLRs)2 and 4 and their roles in inflammatory and apoptotic pathways. We hypothesized that TLR2 and TLR4 coexpression is crucial for eliciting inflammation and apoptosis, whereas TLR4 alone might be insufficient. Our findings revealed that in symptomatic infections, both TLR2 and TLR4 are coexpressed, leading to markedly elevated levels of the proinflammatory cytokines IL-10, IL-1β, TNF-α, and IL-6. This enhanced inflammatory response is further evidenced by increased CD4 expression, indicating robust T helper cell activation. In contrast, asymptomatic infections are characterized by exclusive TLR4 expression, with inflammatory markers remaining at baseline levels. Additionally, we observed that L. interrogans induces apoptosis in symptomatic animals through TLR2 and TLR4 mediated activation of Caspase 8 and Caspase 3. These findings illustrate that L. interrogans drives both inflammation and apoptosis via the combination of TLR2 and TLR4 actions. When only TLR4 is activated, the immune response is insufficient, resulting in an asymptomatic disease course. This study provides novel insights into the differential roles of TLR receptors in leptospirosis, offering potential directions for targeted therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The current study describes the biological synthesis of manganese oxide nanoparticles from Bacillus thuringiensis, as well as their characterization, biological activity, and toxicity. Nanoparticles may be synthesized in multiple ways, but the biogenic process is the most environmentally friendly and cost-effective. The optical, structural, and crystalline properties of the nanoparticles were investigated. A distinctive peak at 246 nm with a band gap of 3.7eV indicates manganese oxide nanoparticle production. A strong peak at 563.09 cm -1 indicates Mn-O stretching in Fourier Transform Infrared Spectroscopy analysis. X-ray diffraction revealed that the crystalline grain size of manganese oxide nanoparticles was 11.23 nm. The agglomerated spherical shape is seen in the Scanning Electron Microscope and High-Resolution Transmission Electron Microscope investigations. The presence of manganese was verified by the EDAX. Manganese oxide nanoparticles have a significant zeta potential peak of -23.4 mV. This work explored the biological activity of manganese oxide nanoparticles, including antibacterial, anti-inflammatory, antioxidant, and biofilm inhibition studies. To investigate cytotoxicity, Allium cepa root tips are treated with manganese oxide nanoparticles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Flaviviruses transmitted by arthropods, including the Murray Valley Encephalitis Virus (MVEV), are RNA viruses capable of causing severe encephalitis in various hosts. The spread of these viruses is closely linked to climatic conditions and the habitats of host and vector species, leading to outbreaks in new geographic regions. Notable encephalitis-causing flaviviruses include Japanese encephalitis virus (JEV), West Nile virus (WNV), and Kunjin virus (KUNV). MVEV, primarily spread by the mosquito Culex annulirostris and amplified by water birds such as egrets and Nankeen night herons, has caused significant outbreaks in Australia, including severe epidemics in 1951, 1956, and 1974. Despite its severity, no rapid diagnostic techniques or effective antiviral treatments are available, and current interventions are limited to supportive care and mosquito management. Given the absence of a licensed vaccine, this study aimed to develop a multi-epitope hybrid vaccine targeting MVEV using in silico approaches. The study focused on identifying B-cell and T-cell epitopes from the MVEV Envelope (E) protein, constructing a vaccine candidate, and computationally validating its immunogenic potential. The designed vaccine underwent rigorous analysis of its antigenic properties, allergenicity, and toxicity. Disulfide engineering and assessment of physicochemical properties ensured the structural integrity of the vaccine, supported by Ramachandran plot and ProSA web analyses. Molecular docking studies assessed the vaccine's binding affinities with TLR-3, and MHC-I. Population coverage analysis of MHC-I and MHC-II epitopes evaluated global efficacy. Additionally, molecular dynamics simulations explored the stability of docked complexes, and PDBsum analysis elucidated interaction details. Immunological simulations were conducted to predict immune response outcomes, providing comprehensive validation of the vaccine's antigenicity. The findings highlight the potential of a multi-epitope vaccine as a viable strategy for MVEV prevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Herein, biocompatible pure tungsten oxide (WO 3 ) and zirconium-doped tungsten oxide (Zr-doped WO 3 ) nanoparticles (NPs) were prepared via a green approach from moringa plants with different doping concentrations (3, 5, and 7 %). The as-synthesized materials were morphologically and optically characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD), Fourier-transform infrared (FTIR), and ultraviolet-visible (UV-Vis) spectroscopy. The FTIR spectra clearly showed that two distinguishing bands at 603 and 674 cm -1 of WO 3 were shifted to a higher wavenumber upon doping with zirconium. EDX analysis confirmed the successful synthesis of pure WO 3 and Zr-doped WO 3 by the green approach. The UV-Vis study exhibited that the bandgap of pure WO 3 is blue-shifted upon Zr doping due to the Burstein-Moss effect. The XRD pattern revealed that the crystalline nature of WO 3 is increased by increasing the Zr content. Further, the as-synthesized materials were evaluated for enzymatic, antibacterial, and antioxidant activities. The enzymatic results showed that 7 % of Zr-doped WO 3 NPs have a higher activity for the α-amylase enzyme. Additionally, 7 % Zr-doped WO 3 also showed better antioxidant activity, up to 85 % for free radical scavenging. The antibacterial performance of 7 % Zr-doped WO 3 is higher as compared to other corresponding samples for different strains of bacteria. These results demonstrated that this facile and novel synthetic route will open a new door for designing an efficient nanomaterial for biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The increase of Arcobacter spp. infection cases in humans, coupled with varying symptomatology, highlights the need to study the virulence mechanisms of these bacteria. Arcobacter butzleri can induce the release of several proinflammatory cytokines in human monocytic-derived macrophages, but the mechanism used to achieve this is still unclear. Therefore, we aimed to investigate the human innate immune response triggered by pathogenic Arcobacter spp., by studying the activation of the human Toll-like receptors (TLRs). Arcobacter skirrowii was the only species that showed the ability to activate all tested TLRs. Arcobacter cryaerophilus demonstrated to be able to activate TLR1/2, TLR4, and TLR2/6. A. butzleri hardly activated the TLRs, only TLR2/6 and TLR1/2 to a small extent. While all the Arcobacter species tested possess flagellum, as shown by motility assays and electron microscopy, only the flagellum of A. skirrowii was able to activate TLR5. The alignment of the flagellin amino acid data revealed that A. skirrowii shares a greater number of crucial amino acids for TLR5 recognition with the FliC of Salmonella than the other Arcobacter species, which might explain why A. skirrowii activates TLR5. Our results demonstrated that the activation of the different TLRs is Arcobacter species dependent, and there might be a correlation between the activation of the TLRs and the pathogenicity of the Arcobacter species., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Itsaso Baztarrika Uria reports financial support was provided by Basque Government. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Multidrug-resistant Acinetobacter baumannii (MDRAB) infections cause elevated rates of patient deaths in intensive care units owing to the high antibiotic resistance of the clinical isolates. The advent of multidrug-resistant A. baumannii (MDRAB) strains and the formation of their biofilms are cause for concern. Tea polyphenols (TPs), which exhibit antimicrobial activity, is an ideal alternative strategy for lowering the incidence of nosocomial bacterial infections. This study was conducted to determine the effects of TPs on MDRAB. The antimicrobial and anti-biofilm activities of TPs against MDRAB were investigated in vitro using the propidium iodide assay, scanning electron microscopy, transmission electron microscopy, crystalline violet staining and real-time quantitative PCR (qPCR). The in vivo anti-biofilm and anti-inflammatory effects of TPs were studied using a rat model of MDRAB biofilm-induced pulmonary inflammation. TPs effectively inhibited the proliferation of MDRAB and damaged its cell membrane. Additionally, they inhibited MDRAB biofilm formation by reducing the content of microbial extracellular polymeric substances and altering the expression of genes related to biofilm formation. Moreover, TPs reduced pathological features of lung injury and alleviated MDRAB biofilm-induced pneumonia in rats with a tracheal cannula, attenuating the inflammatory response by inhibiting NF-κB signaling. Our findings suggest that the anti-biofilm and anti-inflammatory activities of TPs render these naturally active compounds favorable candidates for the treatment of tracheal catheter-related infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The ESKAPE pathogens, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, pose a significant threat to individuals with compromised immune system, including children, people with underlying illnesses and patients primarily infected with viruses. Significant mortality rates have been documented as a consequence of severe pneumonia resulting from bacterial respiratory tract infections. Azanza garckeana has been reported to possess antibacterial and anti-inflammatory activities. This study aimed to determine the antibacterial activity of A. garckeana leaf and bark extracts against P. aeruginosa, K. pneumoniae, A. baumannii, and S. aureus. The broth microdilution method was used to evaluate antibacterial activity. The most active extracts were subjected to phytochemical analysis to identify types of bioactive compounds present using gas chromatograph mass spectrometry (GC‒MS). The effect of the extracts on the integrity of the bacterial membrane was performed using nucleic acid and protein leakage assay. Acetone bark extract was assessed for its potential antibiofilm activity using K. pneumoniae. The toxicity profiling of the most potent extracts was performed using sheep erythrocytes and mouse peritoneal cells. The hexane bark extract exhibited greater potency by inhibiting the growth of S. aureus and A. baumannii at a concentration of 200 μg/mL. GC-MS identified the presence of important bioactive compounds including, β-carotene, 9-hexadecen-1-ol, (Z)-, hexadecanoic acid, methyl ester, and 2,4-di-tert-butylphenol. Acetone bark extract exhibited antibacterial activity through disruption of bacterial membrane integrity, observed through significant nucleic acid and protein leakage. The acetone bark extract displayed promising antibiofilm activity against K. pneumoniae. Importantly, the extracts showed minimal toxicity, demonstrating less than 30 % haemolytic activity in sheep erythrocytes and were not toxic to the mouse peritoneal cells, instead boosting their growth. These findings suggest that A. garckeana may serve as a potential source of antibacterial lead agents for the management of respiratory infections., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stanley Mukanganyama reports financial support was provided by Swedish International Development Cooperation Agency. Reports a relationship with that includes: Has patent pending to. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa is a common human pathogen that is resistant to multiple antibiotics due to its ability to form biofilms. Developing novel nanoformulations capable of inhibiting and removing biofilms offers a promising solution for controlling biofilm-related infections. In this study, we investigated the anti-biofilm activity of rutin-conjugated ZnO nanoparticles (ZnO-Rutin NPs) in pathogenic strains of P. aeruginosa. The synthesized ZnO-Rutin NPs had amorphous shapes with sizes ranging from 14 to 100 nm. The broth microdilution assay revealed that ZnO-Rutin NPs, with an MIC value of 2 mg/mL, exhibit greater antimicrobial activity than ZnO NPs and rutin alone. Based on crystal violet staining, the biofilm inhibition rate by ½ MIC of the conjugated nanoparticles was recorded at above 90 %. The significant reduction in exopolysaccharide (62.75-66.37 %) and alginate (38.3-57.61 %) levels, as well as the formation of thin biofilms in the ZnO-Rutin NP-treated group, confirmed the anti-biofilm potential of these nanoparticles. Additionally, a significant decrease in the metabolic activity and viable cells of mature biofilms was observed after exposure to the conjugated nanoparticles. Furthermore, ZnO-Rutin NPs considerably attenuated the expression of the Las-Rhl quorum-sensing transcriptional regulator genes (lasR and rhlR) in P. aeruginosa by 0.39-0.40 and 0.25-0.42 folds, respectively. This work demonstrated that ZnO-Rutin NPs are remarkably capable of inhibiting the initial stage of biofilm formation and eradicating mature biofilms, suggesting they could be a useful agent for treating P. aeruginosa biofilm-related infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Canine distemper virus (CDV) causes a multisystemic disease with central nervous system involvement in dogs. Little is known about the role of immuno-inflammatory and redox-state biomarkers in the pathogenesis and diagnosis of naturally occurring CDV infection. Thus, the objectives of this study were: 1) to evaluate the potential differences in a profile of cytokines/chemokines, and inflammatory and redox-status biomarkers in serum between dogs with CDV-infection and healthy dogs, and 2) possible correlations between serum/blood and cerebrospinal fluid (CSF) of these biomarkers in dogs with CDV-infection. Two groups of dogs were designed: 10 with CDV-infection, and 10 healthy. A total of 13 cytokines/chemokines, 3 inflammatory (C-reactive protein [CRP], haptoglobin [Hp], and butyrylcholinesterase [BChE]) and 3 antioxidants of redox status (cupric reducing antioxidant capacity [CUPRAC], Thiol, and ferric reducing ability of plasma [FRAP]) were analyzed in serum and CSF samples. Serum IL-7, IL-8, MCP-1, CRP, Hp, FRAP and Thiol levels were higher (P < 0.05) in dogs with CDV compared to controls. There were significant (P < 0.05) correlations only in IL-6 and MCP-1 between CSF and serum. In conclusion, deregulated immune response, raised inflammation, and imbalances of redox homeostasis and antioxidant defense status may play role in the pathophysiological mechanism of neurological form of CDV-infection. The combination of clinical features and cytokine biomarkers (IL-7, IL-8 and MCP-1) might facilitate clinical diagnosis for neural involvement in dogs with CDV. Some cytokine/chemokine (IL-6 and MCP-1) in CSF are highly correlated with those of serum, indicating that serum samples could reflect the possible changes of these analytes in CSF., Competing Interests: Declaration of competing interest None of the other authors have any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The biological properties of herbs and essential oils (EOs), such as their antibacterial, analgesic, anti-inflammatory, antioxidant, and anticancer characteristics, make them widely used in a variety of fields. This research aims to assess the antibacterial efficacy of lavender oil against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). The essential oil from Lavandula spica was extracted via water distillation and characterized by using Gas Chromatography-Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FTIR). Bacterial strains were isolated from burn wounds, confirmed by polymerase chain reaction technique, and were tested using disc diffusion method and Minimum Inhibitory Concentration (MIC) calculations. The study identified 28 components in the EO, with monoterpenes being the predominant. Out of 150 samples, 56 (45.52 %) were positive for P. aeruginosa and 67 (54.47 %) for S. aureus by using standard microbiological techniques including Gram staining, biochemical tests and Polymerase chain reaction technique. P. aeruginosa showed high resistance to cefazolin (100 %) and levofloxacin (83.3 %), while S. aureus was highly resistant to cefoxitin, piperacillin, amoxicillin/clavulanic acid, and ampicillin/sulbactam. The zone of inhibition and MIC for EO against P. aeruginosa were 9.910 ± 0.866 and 2.376 ± 0.352 while for S. aureus were 10.597 ± 0.818 and 0.894 ± 0.073 respectively with significance levels of p > 0.05 and p < 0.01. The study concluded that L. spica EO shows promising antimicrobial activity, particularly against Gram-positive bacteria suggesting its potential for further research and antimicrobial use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Methicillin-resistant Staphylococcus aureus (MRSA) constitutes a significant health concern because it promotes infectious mastitis in dairy animals and poses a hazard risk to humans. Controlling MRSA infections is a growing challenge on a global scale because of the bacteria's toxicity and its capacity to develop multidrug resistance (MDR). Combating against MDR bacteria and the spread of infectious diseases needs natural antibacterial alternatives to minimize the economic losses of mastitis. The average treatment cost in Egypt was highlighted. The antibacterial effect of apple cider vinegar (ACV) against MDR-MRSA isolates was evaluated, also the study aimed at profiling antimicrobial resistance genes in MRSA isolates. The incidence of mastitis in cows was more than in buffaloes, and the average total treatment cost was estimated at 82 million EGP from 2016 to 2021 (around 14 million EGP annually). Of the 22 S. aureus isolates (20 %), of which (59.1 % were from cows and 40.9 % from buffaloes), 19 (86.4 %) were confirmed as MRSA. All MRSA isolates exhibited resistance to clindamycin (94.7 %), then both ampicillin and doxycycline (84.2 %), and ampicillin and sulbactam, erythromycin and Fosfomycin (each, 78.9 %). Vancomycin, ciprofloxacin, and levofloxacin can be used to treat MRSA. The prevalence of MDR was significantly high, with 94.7 % of the cases having multiple antimicrobial resistance (MAR) indices ranging from 0.25 to 0.75. All MRSA isolates tested positive for mecA, 89.5 % for the blaZ gene, 84.2 % for tetM, and 73.4 % for ermB. In vitro, the antibacterial properties of ACV were demonstrated to be superior by our results which demonstrate a zone of inhibition with diameters ranging from 20 to 40 mm detected by Agar well diffusion technique and MIC's (Minimal Inhibitory Concentration) ranging from 2 to 4 μg/ml. Some isolates possess MBC (Minimal Bactericidal Concentration) values at the same MIC. This research proposes the potential of ACV to act as a promising antibacterial alternative against MRSA. This can help minimize the health problem of antibiotic-resistant bacteria and improve the efficiency of dairy farms. Further studies are recommended to determine the proper dosage for field administration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sustainable agriculture is increasingly emphasized, focusing on microorganisms' role in maintaining soil fertility and inhibiting plant pathogens. Seeking novel sources of plant-beneficial bacteria, our study explores insects due to their established associations with plants and bacteria. The insect gut, hosting various bacteria, may hold microbes protecting against fungal infections, particularly plant pathogens. Traditional sources of plant growth-promoting bacteria are the rhizosphere and host plant tissues; however, insects serve as diverse bacterial reservoirs in the environment. This study aimed to identify insect-gut-derived bacteria with antifungal properties and cellulase enzyme production, predicting high plant tissue colonization abilities. Cellulase, crucial for breaking down cellulose, is essential for both industry and the environment. We sought to assess the potential of these bacteria as biocontrol agents against plant pathogenic fungi, with a focus on tomato plants. Bacterial isolates from insect bodies, including Lactococcus lactis, Pantoea ananatis, and Serratia liquefaciens, exhibited robust antifungal properties and cellulase activity. In vitro tests and glasshouse tests, confirmed their ability to inhibit the growth of plant-pathogenic fungi, indicating potential for biological control. Moreover, selected strains demonstrated high cellulase enzyme activity, vital for nutrient competition and rapid colonization of plant surfaces. The study introduces insect-gut-derived bacteria as promising biocontrol agents against plant pathogenic fungi. The identified strains, capable of inhibiting fungal growth and producing cellulase, offer sustainable alternatives to synthetic fungicides for protecting tomato plants. The findings advance agricultural practices by harnessing insect-associated bacteria, contributing to eco-friendly and efficient pest management strategies in modern agriculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As a part of the human skin commensal bacterial community, Staphylococcus aureus contributes to the host's immune system education. Nevertheless, it is also considered as an opportunistic pathogen involved in cutaneous infections or skin pathologies, in particular atopic dermatitis. To switch to a pathogenic behavior, S. aureus uses regulatory mechanisms to collectively produce virulence factors. Deprivation of these factors has emerged as a promising way to prevent or treat Staphylococcal diseases in facilitating the role of the immune system, while preserving the protective one of the commensal communities. This study focuses on the anti-virulent effect of dextran sodium sulfate (DSS) and I-modulia®, two natural products that have already proven their value in skincare. The anti-virulent capacity of DSS was first demonstrated by a dose-dependent inhibition of δ-toxin release, a virulence factor known to be a potent inducer of mast cell degranulation, on in vitro S. aureus cultures at high and low virulent states. A transcriptomic study was then implemented for a comprehensive overview of the anti-virulent impact. The results have shown the downregulation of many transcripts related to host immune evasion (scn, sbi), as well as exotoxins (α,γ-toxin) and adhesins production (map, emp), mostly under the control of SaeRS Two-Component System (TCS), one of the two major virulence regulators in S. aureus. Interestingly, genes related to secretion systems and the synthesis of exo-proteases were significantly downregulated when DSS was used in combination with I-modulia®. The repression of these genes was not previously observed and reflects a broader inhibitory action. We have also demonstrated that the inhibition of virulence factors didn't affect S. aureus viability. Our findings suggest that combining DSS and I-modulia® could be a promising therapeutic strategy to counteract microbial dysbiosis in the treatment of S. aureus skin pathologies in re-empowering the host's natural immune defenses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Escherichia coli (E. coli), a normal intestinal microbiota is one of the most common pathogen known for infecting urinary tract, wound, lungs, bone marrow, blood system and brain. Irrational and overuse of commercially available antibiotics is the most imperative reason behind the emergence of the life threatening infections caused due to antibiotic resistant pathogens. The World Health Organization (WHO) identified antimicrobial resistance (AMR) as one of the 10 biggest public health threats of our time. This harmless commensal can acquire a range of mobile genetic elements harbouring genes coding for virulence factors becoming highly versatile human pathogens causing severe intestinal and extra intestinal diseases. Although, E. coli has been the most widely studied micro-organism, it never ceases to astound us with its ability to open up new research avenues and reveal cutting-edge survival mechanisms in diverse environments that impact human and surrounding environment. This review aims to summarize and highlight persistent research gaps in the field, including: (i) the transfer of resistant genes among bacterial species in diverse environments, such as those associated with humans and animals; (ii) the development of resistance mechanisms against various classes of antibiotics, including quinolones, tetracyclines, etc., in addition to β-lactams; and (iii) the relationship between resistance and virulence factors for understanding how virulence factors and resistance interact to gain a better grasp of how resistance mechanisms impact an organism's capacity to spread illness and interact with the host's defences. Moreover, this review aims to offer a thorough overview, exploring the history and factors contributing to antimicrobial resistance (AMR), the different reported pathotypes, and their links to virulence in both humans and animals. It will also examine their prevalence in various contexts, including food, environmental, and clinical settings. The objective is to deliver a more informative and current analysis, highlighting the evolution from microbiota (historical context) to sophisticated diseases caused by highly successful pathogens. Developing more potent tactics to counteract antibiotic resistance in E. coli requires filling in these gaps. By bridging these gaps, we can strengthen our capacity to manage and prevent resistance, which will eventually enhance public health and patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seneca virus A (SVA) is a newly discovered small nucleic acid virus, which can cause swine blister disease (PVD). Currently, there is no drug or vaccine. Studies have shown that SVA relies on the endolysosomal pathway to accomplish intracellular transport and release, and can disrupt lysosomal homeostasis, but its specific mechanism has not been revealed. At present, there is limited research on vaccines and antiviral drugs for it. Esterase D (ESD), a serine hydrolase, is active against many substrates and plays a role in inhibiting viral replication. However, the specific mechanism of the thioesterase activity of ESD in the signaling pathway is unknown. In this study, we synthesized and screened a novel small-molecule ESD activator, FPD5 (4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4,5-dihydro- 1h -pyrazol-3-yl)phenyl), capable of inhibiting the replication of SVA. To explore the mechanism of action of this process, we demonstrated the direct interaction between ESD and lysosomal membrane protein-1 (LAMP1) by CO-IP; Western blot revealed that FPD5 could activate ESD and exert a protective effect on LAMP1 and lysosomes. The deglutathionization function of ESD was verified by protein glutathione immunoblotting and detection reagents, and the affected cysteine residues were found by point mutation technique. The results showed that FPD5 activated ESD to exert thioesterase activity, reduced glutathionylation cysteine 375 in the LAMP1 and decreased SVA production. This study provides a theoretical basis for the development of small molecule drugs against SVA, and also suggests that the activation of the thioesterase activity of ESD is a new direction for future antiviral drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To analysis the differential composition in vaginal microbial communities following HPV infection in Uygur and Han women, and to Explore the correlation between these difference and the degree of Human Papillomavirus (HPV) infection in Uygur women compared to Han women., Methods: A total of 151 Uygur and Han women, with and without HPV, were studied at Xinjiang Uygur Autonomous Region People's Hospital (June 2021-June 2022). These participants were divided into six groups: Uygur control (CV), Uygur transient infection (TPV), Uygur persistent infection (PPV), Han control (CH), Han transient infection (TPH), Han persistent infection (PPH). Vaginal microbiota diversity and dominant bacteria with or without HPV infection were compared using 16S rDNA sequencing., Results: After HPV infection, vaginal pH increased significantly in Uygur and Han women. Vaginal environment cleanliness decreased notably only in Han women (P < 0.05). In Han women, Lactobacillus and Gardnerella dominated both with or without HPV infection. Prevotella, Streptococcus, and Atopobium decreased, while Sneathia increased significantly in persistent HPV cases. Among Uygur women, Gardnerella, Streptococcus, Prevotella, and Shuttleworthia increased significantly in the TPV group, with lower Lactobacillus compared to CV and PPV groups. Bacterial diversity indices (Chao1, Shannon, Simpson) were significantly lower in TPH compared to CH (P < 0.05), with no significant difference in PPH compared to CH (P > 0.05). Chao1 index was significantly lower in TPH than TPV (P < 0.05), with no difference between PPH and PPV (P > 0.05). CV group's Chao1 index was significantly lower than CH (P < 0.01). PCoA and NMDS analyses showed distinct vaginal microbiota between TPH and TPV groups. LEfSe identified 20 differentially expressed taxa in CH-TPH-PPH comparison and 17 in CV-TPV-PPV., Conclusion: Our study reveals ethnic-specific differences in vaginal microbial responses to HPV infection, with notable alterations in diversity and composition. The differential patterns observed between Uygur and Han women underscore the importance of considering host ethnicity in HPV-related microbial dysbiosis, emphasizing the need for tailored interventions targeting microbial signatures to enhance HPV prevention and management strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Min Guo reports financial support was provided by Special Programme for Natural Science Foundation of Xinjiang Uygur Autonomous Region, China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The invasion of host cells by bacteria, leading to intracellular infections, is a major cause of infection recurrence. Drug-resistant Acinetobacter baumannii (A. baumannii) is one of the most challenging public health issues worldwide, with very limited clinical treatment options available. A. baumannii has been found to be able to invade host cells and proliferate within them in recent studies. In addition to the direct antimicrobial effect of antibiotics, the activation of host autophagic flux also plays an important role in eliminating intracellular pathogens. Herein, this study aimes to evaluate the clearance effect of antibiotics on intracellular A. baumannii both in vivo and in vitro, and explore the relationship between this effect and autophagy. The results showed that intracellular pathogens resulted in a significant increase in the minimum bactericidal concentration, while azithromycin can significantly eliminate intracellular A. baumannii in vitro and in vivo. Notably, 60 μg/mL azithromycin demonstrated intracellular clearance against multidrug-resistant A. baumannii and markedly induced autophagosomes in BEAS-2B cells with a mild stimulation of autophagosomes degradation. These findings indicated that azithromycin can significantly clear intracellular A. baumannii and its ability to clear intracellular A. baumannii may be related to the stimulation of autophagosome formation and the induction of host autophagy, which has important implications for the clinical treatment of A. baumannii infections, especially when intracellular infections are present., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A biofilm is a complex aggregation of microorganisms, either of the same or different species, that adhere to a surface and are encased in an extracellular polymeric substances (EPS) matrix. Quorum sensing (QS) and biofilm formation are closely linked, as QS genes regulate the development, maturation, and breakdown of biofilms. Inhibiting QS can be utilized as an effective approach to combat the impacts of biofilm infection. The impact of biofilms includes chronic infections, industrial biofouling, infrastructure corrosion, and environmental contamination as well. Therefore, a deep understanding of biofilms is crucial for enhancing public health, advancing industrial processes, safeguarding the environment, and deepening our knowledge of microbial life as well. This review aims to offer a comprehensive examination of challenges posed by bacterial biofilms, contemporary approaches and strategies for effectively eliminating biofilms, including the inhibition of quorum sensing pathways, while also focusing on emerging technologies and techniques for biofilm treatment. In addition, future research is projected to target the challenges associated with the bacterial biofilms, striving to develop new approaches and improve existing strategies for their effective control and eradication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Salmonella spp. represent a significant etiological agent of foodborne illnesses and constitute a notable public health challenge on a global scale. Effectively managing Salmonella contamination within the food supply chain is imperative, as it represents a significant threat to public health, potentially leading to severe illnesses with fatal consequences. A novel bio-preservative agent is required to combat Salmonella food contamination during different stages of the food supply chain. Bacteriophages are acknowledged for their safety and recognized for their efficacy in bio-food preservation. Given their consumption together alongside food, it becomes pivotal to assess their potential toxicity concerning the probiotic gut microbiota. In this research, BALB/c mice were employed to evaluate the sub-chronic oral toxicity of bacteriophages targeting Salmonella. Following 28 consecutive days of sub-chronic administration of the Salmonella phage through oral means, histopathological examinations of vital organs, including the lung, kidneys, heart, liver, and intestine, revealed normal organ structures and no significant pathological abnormalities, in both the control and experimental groups. No physical or behavioural change was noticed in the experimental mice. Furthermore, the proliferation of indicative probiotic bacteria persisted unchanged even following a 24-h incubation with the Salmonella phage. The body weight of both the control and experimental subjects, along with a comparative analysis of urine test results, exhibited no variations. Notably, the phages demonstrated no discernible impact on the probiotic microbiota, specifically the Lactobacillus and Bifidobacterium species isolated from the caecum of both mice that received treatment and those that did not. In untreated animals, the probiotic population (mean log CFU/ml) ranged from 1.9 to 2.4 log and 2.4 to 2.5 log, while in treated mice, it ranged from 2.0 to 2.3 log and 2.3 to 2.4 log for the Lactobacillus and Bifidobacterium species, respectively. The results of the investigation indicate that the oral administration of the lytic Salmonella phage showed no observable adverse effects on the animals, indicating an absence of harm., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Naveen Kumar R reports was provided by ICMR - National Institute of Nutrition. Naveen Kumar R reports a relationship with ICMR - National Institute of Nutrition that includes: employment. Naveen Kumar R has patent pending to Not applicable. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study provides a systematic review of 512 reported cases of Nocardia brain infections from 2000 to mid-2024. It focuses on analyzing clinical manifestations, radiological findings, bacterial identification methods, and antibiotic resistance patterns. Special attention is given to the differences in outcomes between immunocompromised and non-immunocompromised patients. We also explored personalized treatment approaches by analyzing outcome-related factors through correlation analysis and linear discriminant analysis. Imaging findings commonly showed brain abscesses, lesions, and mass effects, with a high prevalence of antibiotic resistance. Diagnostic methods using conventional microbiological cultures were less effective compared to advanced molecular diagnostics, which enhanced detection accuracy and reduced time to diagnosis. This review also identifies key factors influencing treatment outcomes, including the timely initiation of appropriate antibiotics, particularly the combination of sulfonamides and β-lactams, as well as the importance of surgical intervention. These findings underscore the necessity of improving diagnostic and therapeutic strategies to achieve early diagnosis and personalized treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhenjun Li reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) form biofilms that contribute to increased antimicrobial resistance, leading to treatment failure and/or relapse. It is, therefore, necessary to develop new antibiofilm strategies to eradicate MRSA biofilms related infections. This study was aimed to evaluate the effect of the combination of quinic acid and kanamycin against the preformed biofilms of methicillin-resistant Staphylococcus aureus., Methods: Broth microdilution method was deployed to evaluate the antibacterial activity. Whereas antibiofilm activity was evaluated by crystal violet staining, 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium-bromide (MTT) assay, and scanning electron microscopy (SEM). The checkerboard method was adopted to assess the combination effects. Quantification of exopolysaccharides was determined by the phenol-sulfuric acid method. The eDNA was quantified by fluorescence spectrophotometry. Cytotoxicity activity was evaluated by the MTT assay on the human embryonic kidney (HEK 293) cell line., Results: Quinic acid, combined with kanamycin, effectively eradicated the methicillin-resistant S. aureus biofilms by effecting biofilm biomass and cell viability. Scanning electron microscopy demonstrated a less adherence of S. aureus cells, - after treatment with quinic acid combined with kanamycin, as compared to each drug alone. The combination of quinic acid and kanamycin thus demonstrated the ability to destroy the exopolysaccharides and eDNA of biofilm matrix without any toxic effect on HEK 293 cells., Conclusion: Our results demonstrated the potential of using quinic acid in combination therapy, with an antibiotic, against infections caused by MRSA strains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacterial co-infection with cutaneous leishmaniasis (CL) can effect on the clinical appearance of lesions and delay the healing process. The pattern of bacterial pathogens involved has rarely been investigated in Iraq. The aim of present study was to identify the bacterial agents contaminating CL and their susceptibility to commonly used antibiotics. Four hundred cases of CL were diagnosed in Salah El-Din General Hospital, Iraq. A total of 424 ulcer samples obtained from 400 patients of CL were cultured, and all isolates were diagnosed based on phenotypic characteristics of colonies, bacterial cells and using biochemical tests. No bacterial growth appeared in 124 cases (29.25 %) of the total number of examined ulcer samples, whereas 300 cases (70.75 %) were contaminated. Both Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes) and Gram-negative bacterial species (Escherichi coli, Klebsiella spp., Pseudomonas aeruginosa) were present. The infection with S. aureus represented the highest percentage (26.42 %), while Ps. aeruginosa had the lowest percentage (2.83 %) compared with other bacterial infections. The sensitivity of the isolated bacteria associated with CL was tested against a number of antibiotics (Amoxicillin, Ampicillin, Cefixime, Chloramphenlcol, Doxycycline, Tetracycline). Resistance to Amoxicillin, Ampicillin, and Cefixime was generally high. While, Chloramphenicol showed absolute effectiveness against isolated bacteria. The results of the current study show that bacterial infections should be considered in diagnosing and treating CL lesions, with Chloramphenicol demonstrating the highest efficiency in treating such bacterial infections. The present study also suggests that hygiene, use of suitable disinfectants, controlling of antibiotic administration and prescription in hospitals and pharmacies must be ensured. In addition, regular surveillance in the endemic area will help control bacterial co-infection and hamper the occurrence of drug-resistant pathogens. The lesion care and management of secondary bacterial infection are essential and anti -leishmanial therapy in CL may be more effective when combined with antibiotics. Future molecular studies are needed to identify the species of Leishmania causing CL in Iraq to gain a better understanding of their clinical manifestations (dry or moist ulcers) and their associated bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Herein, we analyzed the in vitro effect induced by total lipid extracts from Trypanosoma cruzi amastigotes of RA and K98 strains, which were obtained after overnight incubation (RAinc and K98inc) to mimic phospholipid hydrolytic processes that occurred adjacent to degenerating amastigote nests in tissues of Chagas disease patients. We demonstrated that RAinc and K98inc might possess bioactive lipid molecules with anti-inflammatory bias since they inactivated the NF-κB pathway, in contrast to intact lipids. Moreover, different M1/M2 macrophage phenotype markers of polarization were analyzed by RT-qPCR which evidenced that RAinc and K98inc promoted an increased expression of the M2 markers Arginase-1, IL-10, FIZZ and YM-1, and a decreased expression of iNOS and proinflammatory cytokines IL-6 and TNF-α. All these results indicate the relevant role of T. cruzi in bioactive lipid molecules, deepening thus our understanding of their contribution to immunomodulatory mechanisms as well as to macrophage polarization that occurs during the course of Chagas disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Current treatment of Candida infections is threatened by antifungal drug resistance. Thus, medicinal plants have been studied to identify new and highly effective antifungal substances with low toxicity. Here, we showed that the tannin-rich n-butanol fraction of Terminalia catappa (FBuOH) possesses antifungal and antibiofilm properties and protects Tenebrio molitor larvae against Candida albicans infection. FBuOH showed antifungal activity against Candida spp. vaginal isolates (MIC values ranged from 7 to 500 μg/mL). Moreover, a combination of FBuOH with fluconazole (FICI ≤0.5) showed considerably increased anti-yeast, anti-biofilm activity and significantly improved the survival rate (up to 100 %) of T. molitor larvae against C. albicans infection. Furthermore, FBuOH acted synergistically with fluconazole by reducing C. albicans membrane ergosterol content. These results could also explain the synergistic activity between FBuOH and fluconazole, indicating that FBuOH exerted its effects on C. albicans membrane integrity, increasing its permeability. Our findings provide insights into the antifungal activity and low cytotoxicity of FBuOH, showing its potential use as a new antimycotic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Brucellosis is a zoonotic bacterial disease that causes enormous economic losses in livestock populations and severe debilitation in humans globally. This study analyzes the seroprevalence of human brucellosis in Iran from 1970 to 2023, revealing key epidemiological trends based on data from 20,046 individuals. Through serological, culture, and molecular tests, it identifies the Brucella species affecting humans over five decades. The findings emphasize the need for ongoing monitoring and improved disease control efforts. Subsequently, we cultured specimens from seropositive individuals who exhibited suspected symptoms of brucellosis. The specimens included blood (n = 9017), placentas (n = 203), bone marrow (n = 221), aborted fetuses (n = 70), cerebrospinal fluid (CSF) (n = 62), synovial fluid (n = 5), urine (n = 4), sperm (n = 3), lumbar discs (n = 3), abscesses (n = 2), milk (n = 2), and vertebral bodies (n = 1). The overall seroprevalence of brucellosis in Iran was 44.9 % based on RBPT, 20.7 % by SAT, and 8.7 % by 2-ME tests. The highest SAT prevalence occurred in the 2000s (25.8 %), followed by the 1990s (23.8 %), 1980s (22.2 %), 1970s (14.8 %), and 2010s (10.4 %). Two main Brucella species were identified in infected humans as Brucella melitensis and Brucella abortus. Positive culture rates varied by sample type, with 9.9 % for blood, 10.4 % for bone marrow, and up to 100 % for fluids like urine and milk. The most common strain was B. melitensis biovar 1 (89.2 %), while B. abortus biovar 1 had a much lower incidence (0.3 %). This investigation showed that the highest rates of culture positivity were in samples of urine, synovial fluid, abscess, and milk. These findings suggest that B. melitensis continues to be an important public health concern and that recent years of decline may be due to better control measures of the disease. The combined use of serology and culture is recommended for diagnosing brucellosis. Increased awareness among farmers and consumers of raw dairy products, coupled with nationwide control measures, is crucial for combating zoonotic brucellosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The majority of anti-leishmanial drugs used for treating trypanosomatid parasites help to reduce human morbidity and mortality. However, parasites have developed drug resistance, which has made it challenging to treat leishmaniasis. Therefore, new drugs and drug targets need to be identified. Protein synthesis is a crucial anabolic mechanism necessary for parasite survival. Histidyl-tRNA synthetase (HisRS) is an essential enzyme that is required for histidine incorporation into proteins. Recent studies on HisRS have shown differences between trypanosomatid HisRS and human HisRS, which could lead to the development of trypanosomatid HisRS structure-based inhibitors. This study aims to determine the role of L. donovani HisRS (LdHisRS) in parasite growth and virulence in vitro using RNAi. The silencing effect of LdHisRS expression was determined using qPCR. The results showed that after 24 and 48 h of incubation with 90 ng siRNAs, LdHisRS mRNA expression levels were significantly reduced by ∼3.14-fold and ∼3.90-fold, respectively. SiRNA-treated parasites also exhibited ∼46.6 % delayed growth and ∼47 % reduced virulence. Additionally, homology modeling, virtual screening, and molecular docking studies were performed with potential inhibitors that have significant suppressive activity in bacteria, fungi, and viruses. Halofuginone was found to have the best binding affinity of -9.09 kcal/mol as a potent inhibitor against LdHisRS. The molecular dynamics (MD) results showed that halofuginone could interact with the various active site segments, potentially blocking substrate access. The data on gene silencing through siRNA suggests that LdHisRS is essential for the parasite's growth and survival. The computational findings could lead to the development of a potent ligand (halofuginone) as a future anti-leishmanial drug, paving the way for an effective therapeutic treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vikas Kushwaha reports financial support was provided by University Grant Commission, Government of India under the D.S. Kothari Post-Doctoral Fellowship (Grant number.F.4-2/2006 (BSR)/BL/18–19/0387). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mycobacterium tuberculosis (Mtb) is the bacterium responsible for causing Tuberculosis (TB) and understanding its mechanisms of virulence, persistence, and pathogenesis is a global research priority. Attenuated strains of Mtb are valuable tools for investigating the genes and proteins involved in these processes. In this study, we identified an Mtb mutant, H37Rv-S, which exhibits a shorter mycelium, smoother colony, slower growth, and reduced antibiotics resistance compared to the wild-type strain H37Rv. Genomic sequencing revealed 34 mutation events in the coding regions of H37Rv-S, affecting 31 genes. We conducted TMT-labeling quantitative proteomics to compare the expression differences between H37Rv-S and H37Rv, as well as their infected bone marrow derived macrophages (BMDMs). The results showed that 716 protein groups (23.96 %) in H37Rv-S and 115 protein groups (2.99 %) in the infected BMDMs were differentially expressed. The dysregulated proteins in H37Rv-S correspond with its phenotype characteristics. Among the 31 affected genes in H37Rv-S, 10 showed upregulation and 1 showed downregulation at the protein level. Notable, 16 associated network proteins in the phoP/phoR system were significantly dysregulated due to a frameshift mutation in phoP, altering its protein sequence after Phe45. The dysregulated host proteins in H37Rv-S were associated with immune response, necroptosis, and ferroptosis. Additionally, H37Rv-S demonstrated reduced survival capability in strain fluorescence labeling and colony-forming unit (CFU) counting post-infection of BMDM cells. These findings suggest that H37Rv-S is an attenuated strain exhibiting defective phenotype characteristics and is more readily recognized and eliminated by the host. This enhanced understanding of the differences between virulent and attenuated strains could facilitate the development of new targets and therapeutics for TB prevention and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: Plants contain a wide variety of bioactive compounds, which have attracted the interest of researchers in finding novel sources of natural medicine. In the following paper, we aim to evaluate the antibacterial potential of extract fractions associated with Parkia speciosa pods and beans against human pathogenic bacteria., Methods: Antimicrobial activity was determined with disc diffusion and broth microdilution assays against eight skin colonising microorganisms including Staphylococcus aureus, Staphylococcus epidermidis, Salmonella enterica, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia followed by further fractionation of the pods ethyl acetate fraction by column chromatography along with preparative thin-layer chromatography. Quantification of bacterial death mechanism was elucidated by the measurement of hole size in cell wall that has been induced by extract constituents via field-emission scanning electron microscopy (FESEM)., Results: Four fractions showed significant antimicrobial activity against the six microorganisms tested (p < 0.01), with inhibition zones ranging from 35.67 to 17.00 mm, and minimum inhibitory concentration ranging from 6.25 to 50.00 mg/ml in which the pods ethyl acetate fraction was the most effective. The methanol fraction isolated from the pods ethyl acetate fraction was much more effective with a four-fold increase from 6.25 to 1.25 mg/ml against S. epidermidis. The disintegration of S. aureus was due to chronic cell wall alterations with pore creation, invaginations and morphological disorganisation. Autolysis in bacterial cells via the expression of peptidoglycan-disrupting lysozyme or bacterial murein hydrolase was postulated. A significantly large pore with a mean diameter of 293.7 nm was detected in the cell wall of S. aureus., Conclusion: P. speciosa fraction could be a potential novel source for the development of a natural antibacterial agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The exposure risk of plasmid-mediated quinolone resistance (PMQR) genes increases the incidence of resistant bacterial infections, has resulted in clinical treatment failures with ciprofloxacin, necessitating urgent implementation of novel strategies for controlling this situation. Matrine serves as the principal constituent of the traditional Chinese herb Sophora flavescens Ait. and exhibits pharmacological activities including anti-inflammatory, antibacterial, anti-tumor, and hepatoprotective effects. However, the precise mechanism by which matrine exhibits antibacterial activity remains incompletely elucidated. This study investigated the antibacterial potential and synergistic mechanism of matrine in combination with ciprofloxacin against qnrS-carrying E. coli. The clinical ciprofloxacin-resistant E. coli carrying the qnrS and the recombinant E. coli DE3 (pET28a-qnrS) were evaluated for their antibacterial activity in vitro, it was found that the combination of matrine/ciprofloxacin exhibited a significant synergistic, reducing the MIC value of ciprofloxacin against qnrS-positive E. coli by 4-fold, and it effectively reduced the bacterial load to undetectable levels within 10 h without obvious cytotoxicity. Moreover, consistent findings were observed in significantly reducing bacterial load within the mouse infection model. Molecular docking revealed that matrine was localized in the large loop B of the qnrS crystal structure, establishing hydrogen bonds with Thr-102 and Arg-101, thereby disrupting the activity of qnrS. Interaction analysis further confirmed that matrine could significantly inhibit the protective effect of qnrS on gyrase and restore the activity of ciprofloxacin against qnrS-positive E. coli. Matrine may serve as a qnrS inhibitor to restore the efficacy of ciprofloxacin, suggesting its potential as a novel antibiotic adjuvant for controlling bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Camel contagious ecthyma is a highly infectious viral skin disease that affects camels and causes economic losses. This study reports the isolation and the phylogenetic analysis of contagious ecthyma virus among camels in Morocco. The disease was detected in four among fifteen camels with severe papules on the lips and nares. Samples of skin crusts were collected and pooled for virus isolation and titration, PCR testing, and histopathological examination. PCR was used to amplify the B2L gene and the resulting product was sequenced and analyzed genetically. The study's findings indicate the presence of characteristic microscopic changes of poxvirus infection in the examined tissues and the virus was isolated on two cells (lambs testis and Vero) and showed distinct growth patterns. The virus grew rapidly on TA cells and delayed growth on Vero cells. The third passage showed cytopathic effects characterized by cell aggregation. Sequence analysis of the B2L gene revealed 100 % similarity to the camel contagious Ecthyma virus isolated from Ethiopia. The camel virus isolates can be classified into two genetic clades according to the B2L gene sequence: the Asian lineage, which includes isolates from Saudi Arabia, Bahrain, and India, and the African lineage, which includes isolates from the Sudan. In conclusion, this is the first instance of the camel contagious ecthyma virus being identified in North Africa in a herd of camels following exposure to stress. Moreover, the progression of the disease was closely monitored from onset to recovery in a setting without the bacterial complication often observed in the field. The virus exhibited opportunistic behavior, exploiting the stress response. Further studies are warranted to evaluate the pathogenicity of the virus in camels and to genetically characterize the circulating virus from different regions. This will be highly beneficial in the development of an appropriate vaccine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

According to many investigations, persistent oral infections may be caused by oral pathogenic biofilms. Irritation of soft tissues and subsequent bone resorption due to bacterial biofilm contamination of the implant further worsen oral health. Dental problems may be effectively treated using metal nanoparticles (NPs) because they limit the development of many different types of bacteria. With their low toxicity, X-ray sensitivity, high atomic number, near-infrared driven semiconductor qualities, and cheap cost, multifunctional bismuth (Bi) NPs with therapeutic activities show significant potential for the domains of bacterial infection diagnostics and treatment. Also, by directly communicating with the bacterial cell wall, stimulating intracellular effects, inhibiting biofilm formation, producing reactive oxygen species, and inducing adaptive and innate immune responses, BiNPs offer an alternative to conventional antibiotics for treating bacteria with multiple drug resistance (MDR). Hence, BiNPs, which have more antibacterial activity and fewer side effects than chlorhexidine, might be a promising option to fight biofilm-forming bacteria in the mouth. This could lead to their usage in several areas of dentistry. The research delves into the many synthesis techniques of BiNPs and their antibacterial and anticancer capabilities. Next, we'll review how this nanoparticle has helped with dental infections, periodontitis, and dental implant problems. The anticancer effects of BiNPs on oral cancer were also studied. Thus, after this paper, we have highlighted the therapeutic limits and ways to address this issue for the clinical success of BiNPs in promoting oral and dental health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Leishmania is responsible for a neglected tropical disease affecting millions of people around the world and could potentially spread more due to climate change. This disease not only leads to significant morbidity but also imposes substantial social and economic burdens on affected populations, often exacerbating poverty and health disparities. Despite the complexity and effectiveness of the immune response, the parasite has developed various strategies to evade detection and manipulates host cells in favor of its replication. These evasion strategies start at early stages of the infection by hijacking immune receptors to silence critical cellular response that would otherwise limit the pathogen's propagation. Among these receptors, Fc receptors have emerged as a significant player in the immune evasion strategies employed by microorganisms, as they could promote inhibitory pathways. This review explores the potential role of one of these immune receptors, the FcγRIIA, in leishmaniasis and how this parasite may use it and the signaling pathways downstream to evade the host immune response. By understanding the potential interactions between Leishmania and immune receptors such as FcγRIIA, we may identify novel targets for therapeutic intervention aimed to enhance the host immune response and reduce the burden of this disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The present study describes the isolation and separation of isogarcinol and garcinol from kokum fruit by flash chromatography using water (containing 0.1 % formic acid) and methanol mixed with acetonitrile (1:1) with UV detection at 254 nm and was characterised by HR-MS and NMR studies. These were further subjected to antimicrobial studies on Staphylococcus aureus FR1722 and Listeria monocytogenes Scott A by agar diffusion assay and broth microdilution method wherein the MIC (Minimum Inhibitory Concentration) of garcinol and isogarcinol were, 20 μg/mL and 50 μg/mL for S. aureus FR1722 and 50 μg/mL and 100 μg/mL for L. monocytogenes Scott A respectively. Further, studies on the control of biofilm growth were tested using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide) assay followed by Crystal Violet (CV) assay, which showed up to 80 % inhibition. In addition, the biofilm eradication as evaluated by bright field microscopy and the metabolic activity were also carried out against these bacterial strains and the experimental details are presented., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Helicobacter pylori is a common Gram-negative bacterium that inhabits the human stomach and causes a variety of gastric pathologies. One of the growing concerns is its dynamic spread of antibiotic resistance, a process in which biofilm formation is involved. Therefore, it is necessary to find an appropriate, high-throughput research model for the in vivo biofilm development by H. pylori. The aim of the current research report was to determine the usefulness of G. mellonella larvae in assessing the survival of a multidrug-resistant, strong biofilm producing H. pylori strain during its exposure to stress caused by clarithromycin. Using infection models lasting for 3 or 6 days, we confirmed the ability of the tested H. pylori strain to survive in the larvae. We noticed that exposure to clarithromycin significantly reduced the number of cultured bacteria relative to the control, although we did not observe any differences in the number of bacteria using time-lapse, live analysis of fluorescently stained larval hemolymph samples. In conclusion, we confirmed that the examined H. pylori strain can produce biofilm in G. mellonella larvae organism and is able to survive exposure to minimal inhibitory concentrations of clarithromycin (established in vitro) in in vivo conditions. Further refinement of methodologies for monitoring the viability of clinical H. pylori strains in the greater wax moth larvae will enhance the accuracy and reliability of this promising research model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Leptospirosis is a globally important re-emerging zoonotic disease affecting humans and many animal species including dogs. The present cross-sectional study aimed to diagnose acute leptospirosis among 210 suspected dogs using microscopic agglutination test (MAT) and polymerase chain reaction (PCR). Further, epidemiological risk factors were analyzed by univariate analysis and multivariate binomial logistic regression analysis. Out of the 210 dogs, anti-leptospiral antibody was detected in 123 (58.57 %; 95 % CI: 51.6-65.3) dogs by MAT (cut-off titer- ≥1:100), among which 67 (54.47 %; 95 % CI: 45.3-63.4) were seropositive to more than one serogroup. The predominant serogroups were Australis and Autumnalis in the study region. Whereas, acute leptospirosis was established in 49 (23.33 %, 95 % CI: 17.9-29.8) dogs based on ≥ 1:800 titer in unvaccinated dogs and ≥1:1600 titer in vaccinated dogs. The predictive risk factors of acute canine leptospirosis were adult dogs (1-5 years) (p = 0.001), north-east monsoon season (p = 0.011), outdoor management (p = 0.047), history of rodent exposure (p = 0.001) and history of contact with wet soil or stagnant water (p = 0.046). Among 49 acutely infected dogs, thirteen dogs were positive for urine PCR and one dog was positive for both urine as well as plasma PCR. Positive PCR amplicons were identified as Leptospira interrogans based on secY gene sequencing and phylogenetic analysis. This study enlightened about the occurrence of acute leptospirosis among suspected dogs with the above important predictive risk factors, which should be taken into consideration while history taking so that proper treatment strategies can be adopted for early recovery of the animal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Multi-drug resistant Acinetobacter baumannii poses a significant threat to public health. This study investigated the genomic features and phenotypic characteristics of two clinical A. baumannii strains, KBN10P01317 (low-virulent) and KBN10P01599 (high-virulent), which share the same sequence type and antimicrobial susceptibility profile. The phenotypic characteristics of A. baumannii strains were assessed by antimicrobial susceptibility testing and virulence trait examination in vitro and in vivo. Whole-genome sequencing was conducted for comparative genomic analysis, and the expression of virulence-associated genes was analyzed using quantitative polymerase chain reaction. Our comparative genomic analysis revealed that KBN10P01599 harbored a larger genome with a greater number of antimicrobial resistance genes, including two copies of the critical resistance gene bla OXA-23 , which might contribute to its higher minimum inhibitory concentration for carbapenems (64 μg/ml) compared to KBN10P01317 (32 μg/ml). Although both A. baumannii strains possessed the same repertoire of virulence-associated genes, KBN10P01599 exhibited significantly enhanced expression of quorum sensing (abaI/R) and biofilm formation genes (csuCDE, bap, and pgaA), correlating with its virulence traits, including increased surface motility, biofilm formation, and adherence to host cells. The differences in the expression of virulence-associated genes between the two strains were partly attributed to the transposition of insertion sequence elements. These findings provide valuable insights into the genetic basis of the virulence potential and antimicrobial resistance in A. baumannii, highlighting the evolutionary changes that may occur within strains of the same clone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The complex interactions between parasites, their hosts, and associated microbiota hold significant implications for host health and disease outcomes. Helminths like Ascaris lumbricoides and Ascaris suum can significantly alter the host's intestinal microbiota, affecting both parasite biology and host pathology. Despite extensive research on host-microbiota changes due to helminth infections, the study of helminth-associated microbiota remains limited. This study aims to characterize the microbiota associated with Ascaris larvae and surrounding host tissues at distinct developmental stages (day 4, day 8, day 14), during larval migration through the liver, lungs, and intestine, and its impact on the host's microbiota in a murine model. Twenty mice were infected with 2500 embryonated A. suum eggs via oral gavage. Five Ascaris-infected mice and age-matched naïve mice were euthanized at 4-, 8-, and 14-days post-infection (DPI). Stool, intestine, liver, and lung samples were collected. Larvae were isolated from embryonated eggs in vitro, from the liver at 4 DPI, and the lung at 8 DPI. Utilizing 16S rRNA sequencing, we analyzed bacterial diversity in samples from different Ascaris stages and host tissues. Our results revealed a total of 8040 amplicon sequence variants (ASVs) with Ascaris samples displaying the highest diversity. Notably, Ascaris-larvae associated microbiota differed significantly from that of the host, with higher diversity observed in the parasite. Differential abundance analysis identified distinct taxonomic patterns, highlighting specific genera such as Bradyrhizobium, Achromobacter, and Pseudomonas in Ascaris. Our findings suggest that Ascaris harbors a unique microbiota that potentially exchanges bacteria with the host during larval migration. These insights pave the way for further research into the ecological and functional dynamics of helminth-microbiota interactions, which may inform novel therapeutic strategies targeting these microbial relationships to mitigate helminth infections and improve host health outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Understanding Cryptococcus neoformans pathogenesis requires a detailed analysis of the various virulence factors that contribute to its ability to cause disease. Cyclosporine, calcineurin inhibitor, impairs C. neoformans production of a polysaccharide capsule and secretion of urease, which are critical for cryptococcal pathogenesis. Two particularly important virulence factors are the production of cell wall melanin and formation of biofilm. In this study, we investigated cyclosporine's effects on melanin production and biofilm formation in C. neoformans. Initially, we examined melanin production in planktonic cells treated with cyclosporine using an L-DOPA containing melanin-inducing medium. Visual inspection and optical microscopy revealed a notable reduction in the characteristic dark coloration of cultures treated with cyclosporine, which indicate decreased melanin production in daughter cells compared to mother cells. Spectrophotometric analysis also demonstrated a significantly altered ultraviolet-visible (UV/vis) absorption spectra in cyclosporine-treated yeast cells, indicative of structural changes in melanin. Additionally, cyclosporine-treated cells exhibited reduced conductance (P-value < 0.0001), suggesting altered cellular ionic properties. The impact of cyclosporine on biofilm formation and mature biofilm disruption was also assessed. Despite cyclosporine's efficacy in modifying virulence factors during planktonic growth, cyclosporine did not inhibit biofilm formation or melanization under biofilm growth conditions, nor did it disrupt mature biofilms in terms of biomass or metabolic activity. However, there was a significant reduction in extracellular matrix production in cyclosporine-treated non-melanized biofilms. Our findings underscore the complex interplay between cyclosporine and C. neoformans, highlighting its differential effects on melanization and biofilm dynamics, which provides new insights into the shortcomings of cyclosporin for combatting cryptococcosis and informs pathways for future therapeutic strategies against cryptococcosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Rodrigo Almeida-Paes reports financial support was provided by National Council for Scientific and Technological Development. Rodrigo Almeida-Paes and Susana Frases reports financial support was provided by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State. Iara Bastos de Andrade reports financial support was provided by Coordination of Higher Education Personnel Improvement. Joshua Nosanchuk reports financial support was provided by National Institutes of Health. Joshua Nosanchuk reports financial support was provided by USDepartment of Defense. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Isoniazid stands as a frontline antibiotic utilized in the treatment of tuberculosis (TB), predominantly impacting the mycolic acid component within the cell wall of Mycobacterium tuberculosis (Mtb). It also affects the formation of lipoarabinomannan (LAM), an essential glycolipid in the cell envelope of Mtb. Despite the effectiveness of antibiotics for TB treatment, drug tolerance development in mycobacteria frequently stems from their adaptation to the hostile environment within the host, leading to treatment failure. Herein, we investigate mycobacterial adaptation to the isoniazid exposure in the host-mimicked conditions by focusing on the stress response genes (virS, icl1, whiB3, tgs1) and LAM-related genes (lprG, p55, lmeA, mptA, embC). Mtb H37Rv and mono-isoniazid resistant (INH-R) strains were cultivated in the host-mimicked multi-stress condition (MS) with or without isoniazid and the relative expressions of these gene candidates were measured using real-time PCR. In the INH-R strain, treatment with isoniazid in multi-stress conditions caused significant upregulation of tgs1, and LAM precursor-lipomannan (LM) synthesis and its transport genes (lprG, p55, lmeA, embC). In the case of H37Rv, all LAM-related genes and tgs1 were downregulated whereas other stress response genes were upregulated, remarkably in icl1 and whiB3. These findings highlight differences in gene expression patterns between drug-sensitive and resistant strains in multi-stress environments with drug pressure. Notably, stress response genes, particularly tgs1, may play a crucial role in regulating LAM production in the INH-R strain in response to isoniazid exposure. This study enhances our understanding of the mechanisms underlying drug resistance, offering valuable insights that could contribute to the development of new strategies for treating and eliminating TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacterial biofilm, a persistent issue in healthcare equipment and typical infections, is exacerbated by the pathogenesis and antibiotic tolerance of Pseudomonas aeruginosa. This bacterium remains a significant concern in the global healthcare sector. Silver nanoparticles, with their potent antibacterial properties, have emerged as a promising solution. This study, therefore, is of utmost importance as it aims to delve into the parameters influencing the biogenic nanoparticle-assisted regulation of bacterial adherence by Pseudomonas aeruginosa. The nano-sized particles were bioengineered using Hellenia speciosa rhizome extracts, which mainly included biologically active components such as mequinol, 4-hydroxy-3-methylacetophenone, and phenol, 2,6-dimethoxy, supplemented with the formation of silver nanostructured materials. The nanoclusters were characterized by UV-Vis spectrophotometry, X-ray scattering, and scanning electron microscopy (SEM). According to a microtiter plate experiment, the nanoparticle degraded biofilms up to 94.41 % at dosages varied from 0 to 25 μg/ml. The light microscopy study and the interface architecture of biofilm suppression by electron microscopy demonstrated the nano-sized particle's potential to prevent bacterial adherence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the application and clinical significance of different memory phenotypes of γδ T-cell subsets in the clinical diagnosis of pulmonary tuberculosis., Methods: In total, 42 patients with tuberculosis (TB) according to the diagnostic criteria for tuberculosis (WS288-2017) who were treated at the Infectious Diseases Hospital affiliated with Soochow University from February 2023 to July 2023 were enrolled. Additionally, 16 patients with latent TB infection (LTBI) and 20 healthy controls (HCs) were included. Flow cytometry was used to measure the expression levels of γδ T cells, Vδ1 T-cell subsets/Vδ2 T-cell subsets, naive (CD45RA + CD27 + ) cells, central memory (CD45RA-CD27 + ) cells, effector memory (CD45RA-CD27 - ) cells, and terminally differentiated (CD45RA + CD27 - ) cells in the peripheral blood. The expression levels at different stages of TB infection were compared., Results: There were no significant differences in peripheral blood γδ T cells or Vδ1 T cells among the HC, LTBI and TB groups. The proportion of CD45RA-CD27+Vδ2 T cells in TB patients was significantly lower than that in HCs and LTBI patients, but the proportion of CD45RA + CD27-Vδ2 T cells was greater. ROC curve analysis revealed that CD45RA-CD27+Vδ2 T cells (AUC), CD45RA + CD27-Vδ2 T cells (AUC), and the combination of both (AUC) were effective in differentiating TB patients from LTBI patients., Conclusion: The proportions of CD45RA-CD27+Vδ2 T cells and CD45RA + CD27-Vδ2 T cells are potential biomarkers for the diagnosis of active TB infection and are helpful for distinguishing active TB infection from LTBI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Tuberculosis continues to pose a health challenge causing the loss of millions of lives despite the existence of multiple drugs, for treatment. The emergence of drug-resistant strains has made the situation more complex making it increasingly difficult to fight against this disease. This review outlines the challenges associated with TB drug discovery, the nature of Mycobacterium tuberculosis shedding light on the mechanisms that lead to treatment failure and antibiotic resistance. We explore promising drug targets, encompassing inhibition of mycolyarabinogalactan peptidoglycan (MAGP) assembly, mycolic acid biosynthesis, DNA replication, transcription, translation, protein synthesis, and bioenergetics/metabolism pathways. A comprehensive overview of the global pipeline of anti-tuberculosis drugs at various stages of clinical trials, the diverse strategies being pursued to tackle this complex disease. By gaining an understanding of the mechanisms that contribute to resistance development and identifying suitable targets, we can pave the way for more effective treatments and contribute to global efforts to combat drug-resistant tuberculosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nitin Pal Kalia reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The increasing challenge of carbapenem antibiotics resistance caused by Pseudomonas aeruginosa is one of the global healthcare problems. P. aeruginosa is a significant opportunistic infection. For epidemiological reasons, identifying resistance genes is essential, and it is also desirable to quickly identify the techniques for producing carbapenemase enzymes. So, the study aims to determine the prevalence of beta-lactamase encoding genes (blaIMP, blaVIM, bla GIM, and bla SPM) phenotypically and genotypically in P. aeruginosa isolates to address the epidemiological spread of these genes in Baghdad city. The study identified P. aeruginosa isolates from various clinical sources by chemical characterization and VITEK 2 system, the antibiogram test, phenotypic screening carbapenem resistance by Combined disk synergy test (CDST), and conventional PCR were used to detect presence of VIM, IMP, SPM, and GIM genes. Bacterial susceptibility testing revealed (40 %) of isolates were resistant to Imipenem and (85 %) of them positive to CDST. Genotypic screening on phenotypic Metallo-β-lactamase isolates showed that (100 %) isolates contained blaVIM genes, blaGIM genes (88 %), whereas (65 %) isolates carried blaSPM genes. In this investigation, there was no evidence of blaIMP among carbapenem-resistant isolates. The study appeared high prevalence of multi-drug resistance P. aeruginosa isolates that produce carbapenemase enzymes and having β-lactamase genes in local hospitalized patients compared to global ratio. Expanding the sample size and types of enzymes screening in MDR P. aeruginosa should be the main focus in the future research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sawsan M. Kareem reports administrative support was provided by Mustansiriyah University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bats play a crucial role in the ecosystem, yet concerns have arisen regarding their potential as carriers of zoonotic bacteria, including Leptospira spp. Due to the lack of knowledge about the carrier state of bats in Brazil, this study aimed to evaluate the presence of antibodies against Leptospira spp. and its DNA in bats from four Brazilian States (São Paulo, Paraíba, Pernambuco, and Ceará). Bats were captured using mist nets and categorized by sex, age, and species. Antibodies were searched in 22 bats via the microscopic agglutination test (MAT). Additionally, 168 kidney and nine urine samples were subjected to PCR for Leptospira spp. Out of 177 samples tested, two (1.13 %) were positive in PCR, while none showed reactivity in MAT. These results suggest a low prevalence of Leptospira spp. infection in bats, indicating a limited role in transmitting leptospirosis to humans, domestic animals, and wildlife in the studied region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Staphylococcus aureus enterotoxins (SEs) can lead to food poisoning and appear to play a pivotal role in the development and severity of mastitis. This study aimed to evaluate whether the presence and diversity of S. aureus Enterotoxin genes mastitis-causing are associated with the development and severity of mastitis in dairy cows. Comparative analysis of S. aureus isolates from cows with clinical and subclinical mastitis (103 isolates each, CM and SM respectively) was conducted, examining the occurrence of enterotoxins (sea-see, seg-sez, sel26, sel27, sel01 and se02). Clinical isolates exhibited greater diversity, with 14 genes compared to four in subclinical isolates, and higher gene frequency (100 % vs. 86.4 %). Among the classical SEs, only sec (1 %) and sed (4.9 %) were detected in clinical isolates, suggesting a potential insignificance in the development of mastitis. Conversely, the selw and selx genes were among the most prevalent in both clinical and subclinical mastitis isolates. While their role in human food poisoning has not been definitively established, they appear to influence mastitis development. Statistical analysis revealed significant differences in clinical isolates carrying seg, seh, sei, seo, seul1, seul2, selw, and selx genes compared to subclinical isolates, suggesting their potential involvement in the severity of mastitis. Determining the frequency of SE gene and its role in mastitis establishment and in clinical mastitis severity, as well as understanding how enterotoxins contribute to pathogenicity in clinical and subclinical mastitis, is crucial for guiding optimal medical therapy for animals and establishing effective veterinary treatments to mitigate economic losses in the dairy industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Candida auris, a multidrug-resistant fungal pathogen, has emerged as a significant global health threat due to its high transmission and mortality rates, especially in healthcare settings., Objective: This study aimed to establish the larvae of the coleopteran Tenebrio molitor (mealworm) as an in vivo model to evaluate the virulence of different C. auris strains., Methods: T. molitor larvae were inoculated with varying doses and strains of C. auris. Mortality rates were monitored, melanization responses, and phenoloxidase activity were assessed. Histopathological analyses were conducted to observe tissue invasion by the yeast cells. Additionally, a biofilm formation test was included as a complementary analysis to determine if biofilm production would influence the virulence of the C. auris strains., Results: A dose-dependent increase in mortality was observed, with the highest fungal load leading to the highest mortality rates. The study also revealed significant differences in virulence among the strains, with those from Kuwait and the reference strain CBS 10913 showing the highest pathogenicity. Melanization rates were significantly higher in infected larvae, indicating an active immune response. The histopathological analysis revealed the presence of C. auris cells within the tissue of T. molitor larvae. However, the biofilm formation complementary test did not show a significant difference in virulence among the different clades of C. auris., Conclusion: The T. molitor model effectively demonstrated the pathogenic potential and virulence differences of C. auris strains. Strains from Kuwait and the reference strain CBS 10913 exhibited the highest virulence, causing 100 % mortality within 24 h. The model also highlighted significant biofilm formation and melanization responses, correlating with fungal burden. This insect model provides a valuable and cost-effective tool for preliminary virulence screening of clinical yeast strains, offering insights into host-pathogen interactions and the potential for evaluating antifungal treatments in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Multidrug resistant tuberculosis (MDR-TB) have emerged as a global challenge. There are several underlying mechanisms which are involved in causing mycobacterial resistance towards antitubercular agents including post translational modifications, efflux pumps and gene mutations. This resistance necessitates the investigation of complementary therapeutic options including the use of bioactive compounds from plants. Recent studies have focused on recognising and isolating the characteristics of these compounds to assess their potential against MDR-TB. Phytoconstituents such as alkaloids, flavonoids, terpenoids, glycosides, and essential oils have shown promising antimicrobial activity against Mycobacterium tuberculosis. These compounds can either directly kill or inhibit the growth of M. tuberculosis or enhance the immune system's ability to fight against the infection. Some studies suggest that combining phytoconstituents with standard antitubercular medications works synergistically by enhancing the efficacy of drug, potentially lowering the associated risk of side effects and eventually combating resistance development. This review attempts to elucidate the potential of phytoconstituents in combating resistance in MDR-TB which hold a promise to change the course of treatment strategies in tuberculosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mycotoxins negatively impact intestinal cell viability, leading to the depletion of beneficial bacteria and rendering birds susceptible to intestinal infections such as necrotic enteritis (NE). Furthermore, they impair the effective digestion and absorption of nutrients. This study aimed to evaluate the effects of Bacillus licheniformis supplementation on broiler birds exposed to mycotoxins and subsequent necrotic enteritis infection. A total of 280 one-day-old broiler chicks were divided into eight groups and subjected to B. licheniformis supplementation (1 × 10 6  CFU/kg of feed) and mycotoxin exposure (aflatoxin and ochratoxin A, each at 150 ppb). Clostridium perfringens (3 × 10 10  CFU/ml) was later administered to induce necrotic enteritis. This study evaluated body weight, feed intake, relative organ weights, hematological and serum biochemical parameters and performed histopathological examinations of liver, kidney and intestine. All the obtained data was statistically analyzed (P ≤ 0.05). The results demonstrated that B. licheniformis supplementation reduced the susceptibility to necrotic enteritis in broilers initially exposed to mycotoxins. Body weight and feed intake were significantly decreased in groups challenged with mycotoxins and necrotic enteritis, both individually and concurrently, compared to the control group. Relative weights of the liver, kidney and intestine were significantly higher in treatment groups. Hematological analysis revealed significantly lower erythrogram parameters (TEC, Hb, and PCV) in birds fed mycotoxin-contaminated feed, with or without necrotic enteritis. Hepatic and renal biomarkers were significantly elevated, and serum protein levels (total protein, albumin) were significantly lower. In contrast, birds supplemented with B. licheniformis and challenged with either mycotoxins or NE showed no significant differences in body weight, feed intake, erythrogram and leucogram compared to the control group. However, B. licheniformis did not mitigate these effects when supplemented in group with concurrent challenge of mycotoxins and NE, however, intensity of changes was reduced. In conclusion, B. licheniformis supplementation effectively alleviates the pathological changes induced by mycotoxins and necrotic enteritis when presented individually but is not sufficiently effective against the combined challenge of mycotoxins and necrotic enteritis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)