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Background: Clinically important lineages in Klebsiella, especially those expressing multi-drug resistance (MDR), pose severe threats to public health worldwide. They arose from the co-evolution of the vertically inherited core genome and horizontal gene transfers by plasmids, which has not been systematically explored. Methods: We designed KleTy, which consists of dedicated typing schemes for both the core genome and plasmids in Klebsiella. We compared the performance of KleTy with many state-of-the-art pipelines using both simulated and real data. Results: Employing KleTy, we genotyped 33,272 Klebsiella genomes, categorizing them into 1773 distinct populations and predicting the presence of 87,410 plasmids from 837 clusters (PCs). Notably, Klebsiella is the center of the plasmid-exchange network within Enterobacteriaceae. Our results associated the international emergence of prevalent Klebsiella populations with only four carbapenem-resistance (CR) PCs, two hypervirulent PCs, and two hvCR-PCs encoding both carbapenemase and hypervirulence. Furthermore, we observed the ongoing international emergence of blaNDM, accompanied by the replacement of the previously dominant population, blaKPC-encoding HC1360_8 (CC258), during 2003–2018, with the emerging blaNDM-encoding HC1360_3 (CC147) thereafter. Additionally, expansions of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hvCRKP) were evidenced in both populations, driven by plasmids of MDR-hypervirulence convergences. Conclusions: The study illuminates how the global genetic landscape of Klebsiella has been shaped by the co-evolution of both the core genome and the plasmids, underscoring the importance of surveillance and control of the dissemination of plasmids for curtailing the emergence of hvCRKPs. [ABSTRACT FROM AUTHOR]

This study aimed to isolate Streptomyces sp. from Moroccan terrestrial ecosystems and identify bioactive compounds through GC–MS analysis. Antimicrobial activity was assessed against various pathogenic microorganisms including Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 60193, and multi-drug resistant strains comprising Listeria monocytogenes, Klebsiella pneumoniae 19K 929, Proteus sp. 19K1313, Klebsiella pneumoniae 20B1572, Proteus vulgaris 16C1737, and Klebsiella pneumoniae 20B1572. Based on the results of the gene sequencing of gene 16S rRNA and phylogenetic analysis, the E2 isolate belongs to the genus Streptomyces with the highest degree of resemblance (97.51%) to the Streptomyces africanus strain NBRC 101005 (NR_112600.1). The isolate exhibited broad-spectrum antibacterial activity, with maximum efficacy against Klebsiella pneumoniae 20B1572 indicated by an inhibition zone diameter of 22.5 ± 0.71mm and a minimum inhibitory concentration (MIC) of 0.0625 mg/mL. The in vitro antioxidant potential of E2 strain was determined through screening of its ethyl acetate extract against sets of antioxidant assays. The results were indicative of E2 strain displaying strong antioxidant activity against ABTS, DPPH free radicals, and FRAP. Furthermore, there was a high significant correlation (p < 0.0001) between the total phenolic and flavonoid content and antioxidant activities. The GC–MS analysis of the extract identified six volatile compounds, with Eugenol (96%) and Maltol (93%) being the most prominent. Additionally, the HPLC–UV/vis analysis revealed six phenolic compounds: gallic acid, chlorogenic acid, vanillic acid, trans-ferulic acid, ellagic acid, and cinnamic acid. Overall, the study highlights Streptomyces sp. strain E2 as a potential source of potent antimicrobial and antioxidant metabolites, offering promise in addressing antibiotic resistance and oxidative stress-related conditions. [ABSTRACT FROM AUTHOR]

The emergence of critical-priority E. coli, carrying a wide array of resistance and virulence factors through food sources, poses a significant challenge to public health. This study aimed to investigate the potential role of oysters sold in Egypt as a source for E. coli, identify their resistance and virulence-associated gene profiles, and assess associated zoonotic risks. A total of 33 pooled fresh oyster samples were obtained from various retail fish markets in Egypt and examined bacteriologically for the presence of E. coli. Antimicrobial resistance was performed by the disk-diffusion method, and the multiple antibiotic resistance index (MAR) was calculated. All isolates were screened for extended-spectrum beta-lactamase (ESBL) (blaTEM, blaSHV, blaCTX−M, and blaOXA−1), plasmid-mediated AmpC blaCMY−2, and carbapenemases (blaKPC, blaNDM, blaVIM, and blaOXA−48) genes by Polymerase chain reaction. Moreover, the presence of virulence-encoding genes was investigated. The virulent MDR strains were clustered using R with the pheatmap package. The prevalence of E. coli was 72.7% (24 out of 33), with 66.7% of the isolates classified as multi-drug resistant, and 75% exhibited MAR values exceeding the 0.2 threshold. Different antimicrobial sensitivity phenotypes and genotype profiles were identified in E. coli isolates. The most prevalent gene detected among all isolates was blaTEM (22/24, 91.7%). Notably, all non-ESBL producers were positive for blaCMY2. Carbapenem-resistant and carbapenem-intermediate strains were carbapenemase producers, with the predominance of the blaKPC gene (11/24, 45.8%). Remarkably, twelve out of sixteen virulence genes were identified, with papC (21/24, 87.5%) and sfa (16/24, 66.7%) genes being the most prevalent. Most isolates carry virulence genes primarily associated with extra-intestinal pathogenic E. coli (ExPEC) (87.5%) and enteropathogenic (EPEC) (70.8%) pathotypes. Four E. coli isolates exhibit cluster patterns. This study provides the first insight into the emergence of virulent MDR E. coli among oysters in Egypt. It underscores the potential role of oysters as a source for disseminating these strains within aquatic ecosystems, presenting a possible threat to public health. [ABSTRACT FROM AUTHOR]

In this work, a set of thirty‐one novel indole‐selenide derivatives (C1–C31), reported recently as P‐glycoprotein inhibitors against multi‐drug resistance in MCF‐7/ADR cells, have been computationally investigated for the first time by in‐silico approaches, combining 2D‐quantitative structure‐activity relationship based virtual screening (2D‐QSAR‐VS) model, molecular docking, and dynamics simulations. The in‐silico study aims to design new potent molecules with higher anticancer inhibitory activity than observed with in‐vitro assays. The 2D‐QSAR model is built using multiple linear regression (MLR) techniques, and cross‐validated by internal and external parameters, applicability domain (AD) analysis, and Y‐randomization tests, corroborating the Golbreikh and Tropsha criteria. Subsequently, virtual screening was performed on the generated database, considering higher pIC50 values than the most effective in‐vivoC27 inhibitor. Subsequently, molecular docking and dynamics simulations were applied on the selected higher‐scoring ligands showing the best interactions with the PHE643, TYR745, and PRO571 amino acids of the P‐gp receptor (7 A6E), predicting dynamically stable complexes at the time‐scale of 200 ns. The in‐silico outcomes indicate that the selected new ligands have shown promising inhibitory activity for future anti‐cancer therapies, with perspective validating by in‐vitro and in‐vivo studies. [ABSTRACT FROM AUTHOR]

Uropathogenic Escherichia coli (UPEC) associated with urinary tract infection (UTI) frequently develops biofilms, assisting UPEC persistence and resulting in antimicrobial resistance. Thus, biofilm inhibition is important in UTI treatment. This study investigated the antibiofilm efficacy of the hydro-ethanolic extract of Abelmoschus moschatus (AMHE), a traditional Indian medicinal plant, against multidrug-resistant (MDR) UPEC in vitro. Nine clinical MDR-UPEC and E. coli (ATCC25922) were screened for biofilm production by safranine staining. Water:ethanol (3:7) was used to prepare AMHE. Phytocomponents in AMHE were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-ESI-MS). Minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MIC-b) of AMHE were determined by spectrophotometry. Growth curve and time-kill kinetics were performed using standard protocols. Metabolic activity and biofilm biomass were determined by MTT assay and confocal laser scanning microscopy. GraphPad Prism v8.0.2 was used for statistical analysis. An array of phytoconstituents in AMHE, including sesquiterpenes, polyphenols, fatty acids, and phytosterols, were identified. All E. coli isolates at 24 and 48 h of static growth exhibited significant biofilm production (p ≤ 0.0001) with cumulative AMHE MIC; 0.8–3.2 mg/ml and MIC-b; 1.6–6.4 mg/ml, respectively. The highest significant (p ≤ 0.0001) reduction in biofilm biomass and metabolic activity at respective 0.5 MIC of AMHE was observed in 3 selected strains without any effect on planktonic growth compared to untreated controls, which suggested its antibiofilm efficacy. Additionally, presence of farnesol, farnesyl acetate, ambrettolide along with other phytoconstituents in AHME might be responsible for the potential antibiofilm attributes. Therefore, future investigations on AMHE might pave the way towards developing effective antibiofilm therapeutics against UPEC biofilm. [Display omitted] • Bioactive compounds identified from Abelmoschus moschatus hydro-ethanolic extract. • The extract inhibited the growth of clinical MDR E. coli. • Antibiofilm activity was evidenced using sub-inhibitory concentration of the extract. • MTT assay and CLSM imaging authenticated the antibiofilm efficacy against MDR E. coli. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) stands as one of the most lethal malignancies, characterized by a grim diagnosis and prognosis. The emergence of multi-drug resistance poses a significant hurdle to effective therapy. Although previous studies have implicated the long noncoding RNA LYPLAL1-DT in the tumorigenesis of SCLC, the precise role of the highly expressed LYPLAL1-DT in SCLC chemoresistance and the underlying mechanism remain inadequately understood. Methods: cDDP-, VP-16- and PTX-resistant SCLC cells lines were established. The viabilities of SCLC cells were assessed by CCK-8 assay in vitro and xenograft tumor formation assay in vivo. Apoptosis was evaluated by FACS, Western blot and JC-1 fluorescence staining, while autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of LYPLAL1-DT were further investigated by gain- and loss-of-function assays in vitro. Furthermore, the therapeutic efficacy of the combination of venetoclax and HCQ with cDDP, VP-16 or PTX was evaluated by cell line, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice model. Results: Our findings revealed that LYPLAL1-DT is upregulated in chemoresistant SCLC cell lines. Gain- and loss-of-function assays demonstrated that LYPLAL1-DT impairs sensitivity to cDDP, VP-16, or PTX both in vitro and in vivo. Overexpression of LYPLAL1-DT significantly enhanced autophagy and inhibited apoptosis in SCLC cells. Further analyses, including RIP and RNA pull-down assays, revealed that LYPLAL1-DT promotes the expression of BCL2 by sponging miR-204-5p and is implicated in the assembly of the autophagy-specific complex (BECN1/PtdIns3K complex). Combining venetoclax and HCQ with cDDP, VP-16, or PTX effectively mitigated chemoresistance in SCLC cells and suppressed tumor growth in CDX and PDX models without inducing obvious toxic effects. Conclusions: Our findings demonstrate that upregulation of LYPLAL1-DT sequesters apoptosis through the LYPLAL1-DT/miR-204-5p/BCL2 axis and promotes autophagy by facilitating the assembly of the BECN1/PtdIns3K complex, thereby mediating multi-drug resistance of SCLC. The triple combination of venetoclax, HCQ, in conjunction with cDDP, VP-16 or PTX overcomes refractory SCLC, shedding light on a potential therapeutic target for combating SCLC chemoresistance. [ABSTRACT FROM AUTHOR]

Microorganisms are evolving to withstand the effect of antimicrobial agents and thereby pose a global threat known as antimicrobial resistance. Resistance towards multiple drugs due to various intrinsic as well environmental factors leads to an even more dangerous drug resistance property known as multi-drug resistance (MDR). WHO has recognized MDR bacteria as a top global threat as they complicate the treatment and augment mortality and morbidity risks. Gram-negative bacteria produce beta-lactamase enzymes that can hydrolyze beta-lactam antibiotics, impacting drug susceptibility. Stenotrophomonas maltophilia, an opportunistic pathogen, exemplifies MDR due to the production of two types of beta-lactamases. The metallo-beta-lactamase (MBL) L1 produced by the bacteria is a class B1 zinc-dependent MBL that is broadly substrate-specific and is a challenge to the currently available treatment options. This study constructs and analyzes a protein-protein interaction network of L1 beta-lactamase to comprehend its role in the MDR property of the bacteria. The network encompasses 51 proteins including L1 MBL (Smlt2667) and 382 interactions, revealing key players in MDR and potential drug targets. The network analysis aids the discernment of antimicrobial gene impact on cellular function, informing drug discovery strategies. This research addresses the emerging challenge of antibiotic resistance and identifies pathways for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carriage of S. pneumoniae is a global health problem that has been associated with the emergence of severe disease and pathogen dissemination in the community. However, summary data on the carriage rate, antimicrobial susceptibility profile, and determinant factors is lacking. Method: Articles were extensively searched in bibliographic databases and gray literature using entry terms or phrases. Studies meeting eligibility criteria were extracted in MS Excel and exported to STATA version 17 software for statistical analysis. A random-effects model was used to compute the pooled magnitude of the nasal carriage of S. pneumoniae and its multidrug resistance. The heterogeneity was quantified by using the I2 value. Publication bias was assessed using a funnel plot and Egger's test. Sensitivity analysis was done to assess the impact of a single study on the pooled effect size. Result: Of the 146 studies identified, 8 studies containing a total of 3223 children were selected for meta-analysis of the magnitude of the nasal carriage of S. pneumoniae and its multidrug resistance. The overall pooled prevalence of nasal carriage of S. pneumoniae and its MDR status in Ethiopian children was 32.77% (95%CI: 25.1, 40.44). and 31.22% (95%CI: 15.06, 46.84), respectively. The highest resistant pattern of S. pneumoniae was against tetracycline, which was 46.27% (95%CI: 37.75, 54.79), followed by 45.68% (95%CI: 34.43, 57.28) trimethoprim-sulfamethoxazole, while the least pooled prevalence was against chloramphenicol, which was 16.2% (95%CI: 9.44, 22.95). The pooled effect of age less than 5 years old (pooled OR = 1.97; 95% CI: 1.35, 2.88, P < 0.001), co-sleeping habit with others (pooled OR = 2.36; 95% CI: 1.77, 3.66; P < 0.001), sibling (pooled OR = 1.82; 95% CI: 1.14, 2.91, P = 0.01), history of hospitalization (pooled OR = 4.39; 95% CI: 1.86, 10.34, P = 0.001), and malnutrition (pooled OR = 2.18; 95% CI: 1.49, 3.19; P < 0.001) showed a statistical association with S. pneumoniae nasal carriage rate by using the random effect Sidik-Jonkman model. Conclusion: The magnitude of the nasopharyngeal carriage rate and multi-drug resistance status of S. pneumoniae alarms the need for immediate interventions such as strengthening antimicrobial stewardship programs, undertaking national antimicrobial surveillance, one-health initiatives, and national immunization programs. [ABSTRACT FROM AUTHOR]

The global dissemination of multi-drug resistant (MDR) pathogenic bacteria requires the rapid research and development of alternative therapies that can support or replace conventional antibiotics. Among MDR pathogens, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are of particular concern due to their extensive resistance profiles, global dissemination in hospital environments, and their major role in some life-threatening infections. Phages, or some of their components, are recognized as one of the potential alternatives that might be helpful to treat bacterial infections. In this study, we have isolated and characterized four lytic bacteriophages targeting K. pneumoniae strains of Sequence Type (ST) 307 or ST147, two predominant high-risk clones of CR-Kp. Phages, designated vB_KpS_GP-1, vB_KpP_GP-2, vB_KpP_GP-4, and vB_KpP_GP-5, were isolated from sewage wastewater samples. The vB_KpS_GP-1 phage was a siphovirus unable to establish lysogeny with its host, while the other three were podoviruses. While 85.7% of K. pneumoniae strains of ST307 were selectively lysed by the phages vB_KpS_GP-1 or vB_KpP_GP-5, the other two phages were able to lyse all the tested strains of ST147 (n = 12). Phages were stable over a broad pH and temperature range and were characterized by burst sizes of 10-100 plaque forming units and latency periods of 10-50 minutes. Genome sequencing confirmed the absence of antibiotic resistance genes, virulence factors or toxins and revealed that two phages were likely members of new genera. Given their strictly lytic nature and high selectivity towards two of the major high-risk clones of K. pneumoniae, cocktails of these phages could represent promising candidates for further evaluation in in vivo experimental models of K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Background: Synergistic drug combination has been shown to be a way of bypassing drug resistance and reducing the amounts of antimicrobials consumed. As infections caused by multi-drug resistant organisms (MDROs) continue to pose global threat, it is important to search for new antimicrobial combinations of plant origin that are safe and readily available. The objective of this study is to evaluate the synergistic antimicrobial activity of extracts of Morinda lucida fruit and Pterocarpus santalinoides seed against multi-drug resistant (MDR) bacterial isolates Methodology: Morinda lucida and P. santalinoides fruits were plucked and washed clean, and the fruits of P. santalinoides were deseeded to remove the seeds. They were cut into smaller pieces and dried under shade before being milled into smooth powder and extracted with methanol. The clinical bacterial isolates used were MDR Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The phytochemical constituents of the extracts were determined using the standard method. The invitro antimicrobial assay of the extracts was done at a concentration of 50 to 400 mg/ml using the agar well diffusion technique. The minimum inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of each extract were determined using the Checker-board micro-titration method, and the FIC result obtained for each isolate was used to calculate the fractional inhibitory concentration index (FICI) of the combined extracts. The time kill assay was performed to confirm the synergistic and bactericidal activities from the MIC values obtained. Results: The phytochemical analysis revealed that the extracts of both herbal plants contained alkaloids, phenol, tannin, saponin, glycosides, and terpenoids. The antimicrobial assay results showed that the polyherbal combination of the extracts was active against all the MDR bacterial isolates tested with varying zones of inhibition. The mean inhibition zone diameters of individual M. lucida and P. santalinoides ranged from 18.0±0.9mm to 26.0±1.4 mm and 17.0±0.1mm to 24.0±0.2mm respectively, while the MIC ranged from 6.25mg/ml to 12.5mg/ml for M. lucida and 12.5 mg/ml for P. santalinoides. The mean inhibition zone diameter of the polyherbal combination of the two plant extracts ranged from 25.00±00mm to 34.0±0.4mm, which compared favorably with that of levofloxacin control (28.0±0.0mm to 32.00±0.0mm), while their MIC ranged from 0.39mg/ml to 1.56mg/ml. The FIC of M. lucida extract ranged from 0.06mg/ml to 0.25mg/ml while that of P. santalinoides ranged from 0.03mg/ml to 0.13mg/ml. The FICI of combined extracts ranged from 0.09mg/ml to 0.38 mg/ml for all the MDR isolates, which is less than 0.5mg/ml, indicating synergism against all the isolates. The time of kill assay confirmed the synergistic and bactericidal activities with a 3log10 CFU/ml decrease in the number of viable cells within 6 hours of incubation. Conclusion: Our findings showed synergistic antibacterial actions of extracts of M. lucida fruit and P. santalinoides seed against MDR clinical bacterial isolates, comparable to levofloxacin. Combination of these herbal plants may serve as alternative sources of antimicrobial agents for the treatment of infections caused by MDR bacterial pathogens. [ABSTRACT FROM AUTHOR]

Campylobacter jejuni is a causative agent of gastroenteritis in humans worldwide, and wild and domestic poultry carry of this bacterium in their gastrointestinal tract. Molecular studies to determine the pathogenicity, origin, and epidemiological relationships among C. jejuni isolates from poultry such as chicken, turkey, and goose consumed as human food are important for public health and infection control. This study aimed to investigate the prevalence of virulence genes and Enterobacterial Repetitive Intergenic Consensus (ERIC‐PCR) based genotyping of C. jejuni isolates obtained from goose cloacal swab samples. For this purpose, PCR analysis of flaA, racR, dnaJ, pldA, cadF, cdtC, ciaB, cdtB, cdtA, virB11, and wlaN virulence genes and ERIC‐PCR analysis of 50 C. jejuni isolates were performed. The emerged genetic profiles and antimicrobial resistance genes regarding the isolates were interpreted with the existing multi‐drug resistance (MDR) findings. Virulence gene positivity was detected as 88%, 84%, 82%, 82%, 80%, 80%, 72%, 30%, and 18% for flaA, racR, dnaJ, pldA, cadF, cdtC, ciaB, cdtB, and cdtA, respectively. VirB11 and wlaN genes were not detected among the C. jejuni isolates. Virulence genes‐based genotyping revealed that the C. jejuni isolates exhibited 22 profiles (A–V). As a result of ERIC‐PCR analysis, the C. jejuni isolates showed heterogeneous distribution, exhibiting 14 different ERIC‐PCR profiles (Cluster I [Cl‐I]–Cluster XIV [Cl‐XIV]). The MDR positivity was detected in 7 (14%) of the C. jejuni isolates. Tetracycline and ciprofloxacin were the antibiotics most frequently included in the MDR profiles. There was no clear correlation between ERIC‐PCR profiles, virulence gene profiles, and MDR profiles. However, isolates with triple‐MDR resistant to ampicillin, tetracycline, and ciprofloxacin showed significant heterogeneity in both ERIC‐PCR profile and virulence gene‐based genetic profile, all of which were positive for ciaB and flaA genes. These results indicate that carriage of the C. jejuni isolates with high gene prevalence and MDR profiles by geese may pose a risk for Campylobacter infections in humans. [ABSTRACT FROM AUTHOR]

While mangrove ecosystems are rich in biodiversity, they are increasingly impacted by climate change and urban pollutants. The current study provides first insights into the emergence of potentially pathogenic yeasts in Hong Kong's mangroves. Sediment and water samples were collected from ten urban and rural mangroves sites. Initial CHROMagarTM Candida Plus screening, representing the first application of this differential medium for water and soil samples collected from a non-clinical environment, enabled the rapid, preliminary phenotypic identification of yeast isolates from mangroves. Subsequent molecular profiling (ITS and/or 28S nrDNA sequencing) and antifungal drug susceptibility tests were conducted to further elucidate yeast diversity and drug resistance. A diversity of yeasts, including 45 isolates of 18 distinct species across 13 genera/clades, was isolated from sediments and waters from Hong Kong mangroves. Molecular profiling revealed a dominance of the Candida/Lodderomyces clade (44.4%), a group of notorious opportunistic pathogens. The findings also reveal a rich biodiversity of non-Candida/Lodderomyces yeasts in mangroves, including the first reported presence of Apiotrichum domesticum and Crinitomyces flavificans. A potentially novel Yamadazyma species was also discovered. Remarkably, 14.3% of the ubiquitous Candida parapsilosis isolates displayed resistance to multiple antifungal drugs, suggesting that mangroves may be reservoirs of multi-drug resistance. Wildlife, especially migratory birds, may disseminate these hidden threats. With significant knowledge gaps regarding the environmental origins, drug resistance, and public health impacts of pathogenic yeasts, urgent surveillance is needed from a One Health perspective. This study provides an early warning that unrestrained urbanization can unleash resistant pathogens from coastal ecosystems globally. It underscores the necessity for enhanced surveillance studies and interdisciplinary collaboration between clinicians, ornithologists, and environmental microbiologists to effectively monitor and manage this environmental health risk, ensuring the maintenance of 'One Health'. [ABSTRACT FROM AUTHOR]

In this age of emergent resistance to antimicrobial agents, pathogenic fungi are not an exception. Diverse strategies have been implemented to curb rampant fungal infections including screening new drugs and stewardship programs. A plethora of recent studies have proved that phytochemicals are efficacious against pathogenic fungi and have potent antifungal activity. This review examines the use of phytochemicals as possible alternative antifungal agents against dermatophytes particularly Trichophyton spp. Literature search was done using three search engines namely Google Scholar, PubMed and Science Direct limited to the year 2019–2023 only. A total of 30 articles were included and 48 plant extracts were evaluated. The major phytochemicals that proved to be potent antifungals both in vitro and in vivo were terpenoids and phenolics. The antifungal potential of phyto-compounds was significantly elevated by incarnation with nanotechnology. Although much has been done in screening of herbal extracts as possible antifungal agents huge gaps still exist on full characterization of all active herbal extracts with antifungal potential especially against resistant strains, together with their mechanism of action, formulation of pharmaceutical dosage forms and clinical trials. [ABSTRACT FROM AUTHOR]

Contact precautions are recommended when caring for patients with carbapenemase-producing Enterobacterales (CPE), carbapenemase-producing Pseudomonas aeruginosa (CPPA), and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E). Our aim was to determine the interpretation of contact precautions and associated infection prevention and control (IPC) measures in the non-ICU hospital setting for patients with CPE, CPPA or ESBL-E in 11 hospitals in the Southwest of the Netherlands. A cross-sectional survey was developed to collect information on all implemented IPC measures, including use of personal protective equipment, IPC measures for visitors, cleaning and disinfection, precautions during outpatient care and follow-up strategies. All 11 hospitals were invited to participate between November 2020 and April 2021. The survey was filled together with each hospital. All hospitals installed isolation precautions for patients with CPE and CPPA during inpatient care and day admissions, whereas 10 hospitals (90.9%) applied isolation precautions for patients with ESBL-E. Gloves and gowns were always used during physical contact with the patient in isolation. Large variations were identified in IPC measures for visitors, cleaning and disinfection products used, and precautions during outpatient care. Four hospitals (36.4%) actively followed up on CPE or CPPA patients with the aim of declaring them CPE- or CPPA-negative as timely as possible, and two hospitals (20.0%) actively followed up on ESBL-E patients. Contact precautions are interpreted differently between hospitals, leading to regional differences in IPC measures applied in clinical settings. Harmonizing infection-control policies between the hospitals could facilitate patient transfers and benefit collective efforts of preventing transmission of multi-drug-resistant Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

This study continues surveillance of antimicrobial resistance associated with combat injuries in Ukraine. To compare species composition, antibiotic resistance profiles, and emergence of new resistance genes between 2014–2020 and 2022–2023. This was a retrospective multi-centre microbiological survey in Ukrainian hospitals. Antibiotic susceptibility, whole-genome sequencing and multi-locus sequence typing were conducted on 154 organisms obtained from 125 casualties between 2022 and 2023. The data revealed a predominance of Gram-negative bacteria, particularly Acinetobacter baumannii (35.7%), Pseudomonas aeruginosa (14.9%) and Klebsiella pneumoniae (20.7%). High levels of carbapenem resistance were observed among A. baumannii {meropenem 72.2% [39/54, 95% confidence interval (CI) 58.4–83.5]; imipenem 66.7% (36/54, 95% CI 52.5–78.9)}, K. pneumoniae [meropenem 90.6% (29/32, 95% CI 75.0–98.0); imipenem 81.2% (26/32, 95% CI 63.6–92.8)] and P. aeruginosa [meropenem 47.8% (11/23, 95% CI 26.8–69.4); imipenem 60.8% (14/23, 95% CI 38.5–80.3)] strains. A. baumannii sequence type (ST)-78 and ST-400 were prevalent from 2014 to 2020, while five strains of ST-1077 were newly identified in 2022–2023. P. aeruginosa strains showed diversity across 16 STs, with ST-773 increasing in frequency and new STs emerging, but lacking carbapenemase genes. K. pneumoniae exhibited increased genetic diversity over time, with three STs from 2014 to 2020 and six new STs, including bla NDM-1 , bla OXA-48 and bla KPC2 carriers, in 2022–2023. The prevalence of multi-drug-resistant isolates with STs associated with a high risk of global dissemination is increasing. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as Pseudomonas aeruginosa. During the chronic long-lasting lung infections, P. aeruginosa adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair system, resulting in an increased spontaneous mutation rate, represents a way to boost the rapid adaptation frequently encountered in CF P. aeruginosa isolates. We selected 609 isolates from 51 patients with CF chronically colonised by P. aeruginosa to study, by full-length genome sequencing, the longitudinal evolution of the bacterium. We recovered at least one hypermutable (mutator) isolate in 57% of patients. By combining genomic information and phenotypic analyses, we followed the evolutionary pathways of the P. aeruginosa mutator strains, identifying their contribution to multi-drug resistance and the emergence of new sub-lineages. By implementing patient clinical data, we observed that mutators preferentially follow a specific evolutionary trajectory in patients with a negative clinical outcome and that maintenance antibiotic polytherapy, based on alternating molecules, apparently reduces the occurrence of hypermutability. Finally, we draw attention to the possibility that modulator-induced changes in the pulmonary environment may be associated with the onset of hypermutability. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to retrospectively investigate an outbreak of linezolidresistant Staphylococcus epidermidis (LRSE), at Tours University Hospital between 2017 and 2021. Methods: Twenty of the 34 LRSE isolates were included in the study. Antimicrobial susceptibility testing was performed using the disk diffusion method and MICs of last-resort antibiotics were determined using broth microdilution or Etest®. Seventeen of the 20 resistant strains were sent to the French National Reference Centre for Staphylococci to determine the mechanism of resistance to linezolid. The clonal relationship between LRSE strains was assessed by PFGE and the sequence type determined by MLST. We retrospectively evaluated a new typing tool, IR-Biotyper®, and compared its results to PFGE to evaluate its relevance for S. epidermidis typing. Medical records were reviewed, and antibiotic consumption was determined. Search for a cross transmission was performed. Results: All LRSE strains showed high levels of resistance to linezolid (MICs = 256 mg/L) and were multi-drug resistant. Linezolid resistance was associated with the 23S rRNA G2576T mutation and none of the 17 strains analyzed carried the cfr gene. Ninety-five percent of the 20 LRSE studied strains were genetically related and belonged to sequence-type ST2. The dendrogram obtained from IR-Biotyper® showed 87% congruence with the PFGE analysis. Prior to isolation of the LRSE strain, 70% of patients received linezolid. No patients stayed successively in the same room. Conclusion: Linezolid exposure may promote the survival and spread of LRSE strains. At Tours University Hospital, acquisition of the resistant clone may also have been triggered by hand-to-hand transmission by healthcare workers. In addition, IR-Biotyper® is a promising typing tool for the study of clonal outbreaks due to its low cost and short turnaround time, although further studies are needed to assess the optimal analytical parameters for routine use. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii, an opportunistic pathogen has shown an upsurge in its multi-drug resistant isolates. OmpA of A. baumannii induces incomplete autophagy and apoptosis in host cells. Various therapeutic alternatives are under investigation against A. baumannii. Here, the major emphasis has been laid on comparing the efficacy of AgNP with different capping agents. OmpA targeted lead, Ivermectin capped AgNP (IVM-AgNP) has been compared with the antibacterial polyvinylpyrrolidone capped AgNP (PVP-AgNP) for their role in the modulations of host autophagy. Upregulation of p62 and LC3B confirmed by real-time PCR analysis indicated an increased autophagic flux upon the treatment with AgNPs. The elongation and closure of autophagic vacuoles was also supported by upregulated Atg genes (Atg4, Atg3, Atg5) in A. baumannii infected cells after treatment with AgNP. Autophagic flux increased on treatment with PVP-AgNP as suggested by the rise in mcherryLC3B fluorescence in A549 cells treated with PVP-AgNP as compared to the GFP-LC3B of IVM-AgNP. This suggests that PVP-AgNP treatment more effectively promotes the elongation and maturation stages of autophagy by increasing autophagic flux. These results indicate that capped AgNPs have the efficiency to revert the incomplete autophagy induced by A. baumannii back to normal autophagic levels. [ABSTRACT FROM AUTHOR]

Cefiderocol is a novel cephalosporin–siderophore conjugate antibiotic that holds promise to thwart infections caused by multi-drug-resistant gram-negative bacilli. Its antibacterial activity against normally susceptible species is not affected by most β-lactamases, including metallo-β-lactamases. Due to the siderophore-mediated entry into the cell, the activity of cefiderocol is less affected by porin loss or active efflux resistance than many other β-lactam antibiotics. The aim of this study was to assess in vitro susceptibility to the cefiderocol of carbapenemase-producing gram-negative bacilli from clinical samples of hospitalized patients. We analyzed 102 clinical strains of carbapenemase-producing Enterobacterales and non-fermentives from hospital centers in Łódź, Poland. Antimicrobial susceptibility to cefiderocol was tested by the minimum inhibitory concentration test strips and disc diffusion methods. The obtained results turned out to be ambiguous, and the area of technical uncertainty made their interpretation very difficult. The cost of therapy with this antibiotic, and difficulties in interpreting the drug susceptibility are the limitations to the use of cefiderocol. Intensive work should be carried out to finally standardize an easily accessible and reliable method for the determination of susceptibility to cefiderocol. [ABSTRACT FROM AUTHOR]

This study reports the isolation and characterization of a Streptomyces sp. from soil, capable of producing bioactive secondary metabolites active against a variety of bacterial human pathogens. We targeted the antimicrobial activity against Escherichia coli ATCC-BAA 2469, a clinically relevant strain of bacteria harbouring resistance genes for carbapenems, extended spectrum beta-lactams, tetracyclines, fluoroquinones, etc. Preliminary screening using the spot inoculation technique identified Streptomyces sp. NP73 as the potent strain among the 74 isolated Actinomycetia strain. 16S rRNA gene and whole genome sequencing (WGS) confirmed its taxonomical identity and helped in the construction of the phylogenetic tree. WGS revealed the predicted pathways and biosynthetic gene clusters responsible for producing various types of antibiotics including the isolated compound. Bioactivity guided fractionation and chemical characterization of the active fraction, carried out using liquid chromatography, gas chromatography-mass spectrometry, infra-red spectroscopy, and nuclear magnetic resonance spectroscopy, led to the tentative identification of the active compound as Pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-, a diketopiperazine molecule. This compound exhibited excellent antimicrobial and anti-biofilm properties against E. coli ATCC-BAA 2469 with an MIC value of 15.64 µg ml−1, and the low cytotoxicity of the compound identified in this study provides hope for future drug development. [ABSTRACT FROM AUTHOR]

Escherichia coli is widely used as an indicator of recent faecal pollution of water. Most E. coli strains are commensals; however, isolates in water samples have been shown to carry antibiotic resistance determinants. In total, 47 E. coli were isolated from selected drinking water sources in Mbarara, Uganda. The isolates were examined for their susceptibility to seven antibiotics and the presence of nine antibioticresistance genes (mostly β-lactamase genes) and class 1 integrons. Isolates showed a high resistance to ampicillin of 55.5% and a high sensitivity to azithromycin and gentamicin at 98 and 96%, respectively. PCR analysis showed the presence of extended-spectrum β-lactamase genes blaCTX-M-32 and blaCMY-2 in 64 and 36% of the isolates. The carbapenemase genes blaOXA-48, blaVIM-2, blaNDM-1, and blaKPC-3 were either not detected or only in a very small number of the isolates, whereas class 1 integrons were present in 68% of the isolates. This study proves that antimicrobial resistance exists in E. coli in water used for drinking purposes in Mbarara city. There is a need for public health actors to improve the surveillance of microbiological quality of drinking water to minimize health risks. [ABSTRACT FROM AUTHOR]

Microbial pathogenesis contributes a significant proportion to the global human mortality rate. Further, the outbreak of antimicrobial-resistant strains represents an alarming threat to human and animal healthcare, which drives scientific research on searching for novel antimicrobials. The present study is one such initiative to isolate new classes of antibiotics from the marine actinomycetes to combat the perpetual increase of multidrug-resistant strains. The soil samples from Tamil Nadu, India's coastal regions, were collected, and eight isolates of the actinomycete species (S1, S1b, S2, S3, S4b, S4W, S4R, S5) were recovered. From their 16S rRNA sequencing, the isolates belonged to Streptomyces sp.; the phylogenetic tree was constructed through the neighbour-joining method. Further, the secondary metabolites of all the isolates were screened against ATCC strains, Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25927) and Acinetobacter baumanni (ATCC 19606) and multidrug-resistant (MDR) strains, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), carbapenem-resistant Klebsiella pneumonia (OXA) and colistin-cephalosporin resistant Escherichia coli (MCR). Of the eight isolates, S1b and S3 showed good inhibition for all the strains tested and their genomic sequences were sequenced and submitted to Genbank, MK641472 (S1b) & MK641473 (S3). Conclusively, their metabolites were purified using LC-MS and no resemblances were found with standard classes of antimicrobials such as nitrofurans, sulfonamides, fluoroquinolones, tetracyclines, chloramphenicols or ivermectins, which suggests that these metabolites are novel and could be exploited for the prospective antimicrobial research. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) infections have become a major global issue in the healthcare sector. Alternative viable tactics for combating bacterial infections, such as the use of bacteriophages, can be considered. One of the major challenges in phage therapy is the emergence of phage-resistant bacteria. This study isolated bacteriophages from water and soil samples against MDR-KP isolates. Susceptible bacterial hosts were exposed to phages at different concentrations and prolonged durations of time to obtain phage-resistant survivors. Phenotypic changes such as changes in growth rates, biofilm formation ability, antibiotic sensitivity patterns, and outer membrane proteins (OMPs) profiling of the survivors were studied. Our findings indicate that the phage ØKp11 and ØKp26 survivors had reduced growth rates and biofilm formation ability, altered antibiotic sensitivity patterns, and reduced OMPs expression compared with the parent MDR-KP002 isolate. These results suggest that the alternations in the bacterial envelope result in phenotypic phage resistance among MDR bacterial isolates. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa is a key pathogen in cystic fibrosis (CF) associated infections, known for its biofilm-forming ability and resistance to multiple antibiotics. Understanding the relationship between biofilm production and antibiotic resistance profiles in clinical isolates can guide treatment strategies. Aims and Objectives: The aims of this study were to investigate the biofilm-forming abilities and antibiotic resistance profiles of clinical P. aeruginosa isolates from patients with CF and to determine the relationship between these two factors and their impact on treatment efficacy. Materials and Methods: A cross-sectional study was conducted on 100 clinical isolates of P. aeruginosa from CF patients. Biofilmforming capacity was categorized as strong, moderate, or weak based on quantitative assays. Antibiotic resistance was assessed for ciprofloxacin, tobramycin, ceftazidime, meropenem, and piperacillin/tazobactam. Multi-drug resistance was defined as resistance to three or more antibiotic classes. Statistical correlations between biofilm-forming capacity and resistance levels were evaluated using the Chi-square tests. Results: Fifty-six percentages of isolates were strong biofilm producers, while 34% and 10% were moderate and weak producers, respectively. The highest antibiotic resistance was observed against ciprofloxacin (60%), followed by tobramycin (50%) and ceftazidime (45%). Forty percentages of the isolates were classified as multi-drug resistant. Strong biofilm producers demonstrated a significantly high correlation with antibiotic resistance (P<0.05). Two predominant clonal groups were identified among the isolates, suggesting a possible clonal spread of resistance traits. Conclusion: The study confirms a strong association between robust biofilm production and heightened antibiotic resistance in P. aeruginosa isolates from CF patients. These findings highlight the need for targeted therapeutic strategies to disrupt biofilm formation and curb resistance spread. [ABSTRACT FROM AUTHOR]

Background: Infection is a common cause of mortality within intensive care units (ICUs). Antibiotic resistance patterns and culture data are used to create antibiograms. Knowledge of antibiograms facilitates guiding empiric therapies and reduces mortality. Most major hospitals utilize data collection to create hospital-wide antibiograms. Previous studies have shown significant differences in susceptibility patterns between hospital wards and ICUs. We hypothesize that institutional or combined ICU antibiograms are inadequate to account for differences in susceptibility for patients in individual ICUs. Methods: Culture and susceptibility data were reviewed over a 1-year period for 13 bacteria in the following ICUs: Surgical/Trauma, Medical, Neuroscience, Burn, and Emergency department. Antibiotic management decisions are made by individual teams. Results: Nine species had sufficient data for inclusion into an All-ICU antibiogram. E coli and S aureus were the most common isolates. Seven species had significant differences in susceptibility patterns between ICUs. E cloacae showed higher rates of resistance to multiple antibiotics in the STICU than other ICUs. P aeruginosa susceptibility rates in the NSICU and BICU were 88% and 92%, respectively, compared to 60% and 55% in the STICU and MICU. Cephalosporins and Aztreonam had reduced efficacy against E coli in the NSICU, however remain effective in other ICUs. Conclusions: The results of this study show that different ICUs do have variability in antibiotic susceptibility patterns within a single hospital. While this only represents a single institution, it shows that the use of hospital-wide antibiograms is inadequate for creating empiric antibiotic protocols within individual ICUs. [ABSTRACT FROM AUTHOR]

There is little information available on antibiotic resistance (ABR) within shrimp aquaculture environments. The aim of this study was to investigate the presence of antibiotic resistance genes (ARGs) in shrimp farming operations in Atacames, Ecuador. Water samples (n = 162) and shrimp samples (n = 54) were collected from three shrimp farming operations. Samples were cultured and a subset of isolates that grew in the presence of ceftriaxone, a third-generation cephalosporin, were analyzed using whole-genome sequencing (WGS). Among the sequenced isolates (n = 44), 73% of the isolates contained at least one ARG and the average number of ARGs per isolate was two, with a median of 3.5 ARGs. Antibiotic resistance genes that confer resistance to the β-lactam class of antibiotics were observed in 65% of the sequenced isolates from water (20/31) and 54% of the isolates from shrimp (7/13). We identified 61 different ARGs across the 44 sequenced isolates, which conferred resistance to nine antibiotic classes. Over half of all sequenced isolates (59%, n = 26) carried ARGs that confer resistance to more than one class of antibiotics. ARGs for certain antibiotic classes were more common, including beta-lactams (26 ARGs); aminoglycosides (11 ARGs); chloramphenicol (three ARGs); and trimethoprim (four ARGs). Sequenced isolates consisted of a diverse array of bacterial orders and species, including Escherichia coli (48%), Klebsiella pneumoniae (7%), Aeromonadales (7%), Pseudomonadales (16%), Enterobacter cloacae (2%), and Citrobacter freundii (2%). Many ARGs were shared across diverse species, underscoring the risk of horizontal gene transfer in these environments. This study indicated the widespread presence of extended-spectrum β-lactamase (ESBL) genes in shrimp aquaculture, including blaCTX-M, blaSHV, and blaTEM genes. Increased antibiotic resistance surveillance of shrimp farms and identification of aquaculture operation-level risk factors, such as antibiotic use, will likely be important for mitigating the spread of ARGs of clinical significance. [ABSTRACT FROM AUTHOR]

One of the primary opportunistic pathogens that can cause a wide range of diseases is Pseudomonas aeruginosa. This microorganism can become resistant to practically every antibacterial currently in use, including beta-lactam antibiotics. Its ability to proliferate as biofilm has been linked to, among other things, the failure of antimicrobial therapies. Due to a variety of virulence factors and host immune system modifications, P. aeruginosa is one of the most significant and common bacteria that colonize wounds and burns. A novel therapeutic option for treating these multidrug-resistant (MDR) bacterial infections is the combination of antibiotics and bacteriophages. This approach has been linked to improved biofilm penetration, a decreased selection of antibiotic and bacteriophage resistance, and an enhanced antibacterial impact. Combining the F1Pa bacteriophage and beta-lactam antibiotics reduced the viability of the mature biofilm of MDR P. aeruginosa strains and suppressed bacterial growth in vitro. F1Pa critically reduced the amount of biofilm that MDR P. aeruginosa clinical strains formed in the in vitro wound model. These findings highlight the bacteriophage F1Pa's therapeutic potential as a prophylactic topical treatment against MDR pseudomonal infections in wounds and burns. [ABSTRACT FROM AUTHOR]

Pasteurella multocida is a Gram-negative bacterium causing economically significant diseases in cattle. This study aimed to determine P. multocida susceptibility to different antibiotics and antibiotic alternatives. In this study, 246 samples (180 nasal swabs and 66 lung tissue specimens) were collected from cattle showing respiratory manifestations in Egypt. Suspected P. multocida colonies following culture were subjected to polymerase chain reaction (PCR) for molecular confirmation of the isolates. A multiplex PCR was employed to identify P. multocida capsular groups. Susceptibility of the isolated P. multocida to different antibiotics and nanoparticles as antibiotic alternatives including silver (AgNPs), chitosan (CNPs) and curcumin (CurNPs) were tested using broth microdilution method. Thirty-two P. multocida isolates were obtained, kmt1 gene was detected in these isolates, and molecular capsular types classification revealed that all isolates were belonged to the capsular type A. Based on broth microdilution method findings, 20 (62.50%) isolates were considered as multi-drug resistant (MDR); the isolates were most sensitive to danofloxacin and kanamycin, whereas they were most resistant to doxycycline and tilmicosin. Antibiotic alternatives showed high anti-microbial activity against tested isolates with minimum inhibitory concentrations ranging from 1.56 - 6.25 µg mL-1, 156 - 625 µg mL-1, and 128 - 512 µg mL-1 for AgNPs, CNPs and CurNPs, respectively. Our finding demonstrated that MDR P. multocida was evident in cattle in Egypt. Although antibiotic alternatives showed promising in vitro anti-microbial effects against MDR isolates, additional studies are required to be actually applicable in veterinary practices. [ABSTRACT FROM AUTHOR]

Diabetes and multidrug-resistant (MDR) bacterial infections remain very common worldwide. This study investigated the antioxidant, antibacterial, and antidiabetic potentials of silver nanoparticles (AgNPs) from Cymbopogon citratus aqueous leaf extract (CCALE). AgNPs were synthesized in a 9:1 of 1 mM AgNO3 solution to CCALE. The synthesis was monitored via colour change and UV-visible spectrophotometry and later characterized using Fourier transform infrared spectroscopy (FTIR), energy dispersive x-ray (EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Using standard procedures, gas chromatography-mass spectrometry (GC-MS) and antioxidant assays (reducing power, ferric reducing antioxidant power, total antioxidant capacity, and DPPH radical scavenging) of AgNPs were performed. Antibacterial activities against MDR bacterial isolates were assessed using the agar-diffusion method. Molecular docking studies were conducted using PyRx and Biovia Discovery Studio with 3D conformers of CCALE phyto-compounds retrieved from PubChem and 11-β-hydroxysteroid and Vaspin proteins from the RCSB Protein Data Bank. The AgNPs showed a light brown colour and a UV-Vis absorption peak at 445 nm. TEM revealed spherical particles (9.22 to 12.54 nm). EDX confirmed significant silver content. FTIR indicated the presence of alkynes, carboxylic acids, and alcohol groups. XRD showed diffraction peaks at 2θ = 38°, 44.5°, and 64.5°, corresponding to the (111), (200), and (220) reflection planes. TGA indicated volatility and thermal stability. The AgNPs demonstrated strong antioxidant and antibacterial activities, particularly against Klebsiella pneumoniae, Salmonella typhi, and Staphylococcus aureus. Stigmasterol exhibited the best binding affinity with the protein targets, suggesting CCALEAgNPs as a potential antioxidant, antibacterial, and antidiabetic drug candidate. [ABSTRACT FROM AUTHOR]

Abstract Background Clinically important lineages in Klebsiella, especially those expressing multi-drug resistance (MDR), pose severe threats to public health worldwide. They arose from the co-evolution of the vertically inherited core genome and horizontal gene transfers by plasmids, which has not been systematically explored. Methods We designed KleTy, which consists of dedicated typing schemes for both the core genome and plasmids in Klebsiella. We compared the performance of KleTy with many state-of-the-art pipelines using both simulated and real data. Results Employing KleTy, we genotyped 33,272 Klebsiella genomes, categorizing them into 1773 distinct populations and predicting the presence of 87,410 plasmids from 837 clusters (PCs). Notably, Klebsiella is the center of the plasmid-exchange network within Enterobacteriaceae. Our results associated the international emergence of prevalent Klebsiella populations with only four carbapenem-resistance (CR) PCs, two hypervirulent PCs, and two hvCR-PCs encoding both carbapenemase and hypervirulence. Furthermore, we observed the ongoing international emergence of bla NDM, accompanied by the replacement of the previously dominant population, bla KPC-encoding HC1360_8 (CC258), during 2003–2018, with the emerging bla NDM-encoding HC1360_3 (CC147) thereafter. Additionally, expansions of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hvCRKP) were evidenced in both populations, driven by plasmids of MDR-hypervirulence convergences. Conclusions The study illuminates how the global genetic landscape of Klebsiella has been shaped by the co-evolution of both the core genome and the plasmids, underscoring the importance of surveillance and control of the dissemination of plasmids for curtailing the emergence of hvCRKPs.

Abstract The emergence of critical-priority E. coli, carrying a wide array of resistance and virulence factors through food sources, poses a significant challenge to public health. This study aimed to investigate the potential role of oysters sold in Egypt as a source for E. coli, identify their resistance and virulence-associated gene profiles, and assess associated zoonotic risks. A total of 33 pooled fresh oyster samples were obtained from various retail fish markets in Egypt and examined bacteriologically for the presence of E. coli. Antimicrobial resistance was performed by the disk-diffusion method, and the multiple antibiotic resistance index (MAR) was calculated. All isolates were screened for extended-spectrum beta-lactamase (ESBL) (bla TEM, bla SHV, bla CTX−M, and bla OXA−1), plasmid-mediated AmpC bla CMY−2, and carbapenemases (bla KPC, bla NDM, bla VIM, and bla OXA−48) genes by Polymerase chain reaction. Moreover, the presence of virulence-encoding genes was investigated. The virulent MDR strains were clustered using R with the pheatmap package. The prevalence of E. coli was 72.7% (24 out of 33), with 66.7% of the isolates classified as multi-drug resistant, and 75% exhibited MAR values exceeding the 0.2 threshold. Different antimicrobial sensitivity phenotypes and genotype profiles were identified in E. coli isolates. The most prevalent gene detected among all isolates was bla TEM (22/24, 91.7%). Notably, all non-ESBL producers were positive for bla CMY2. Carbapenem-resistant and carbapenem-intermediate strains were carbapenemase producers, with the predominance of the bla KPC gene (11/24, 45.8%). Remarkably, twelve out of sixteen virulence genes were identified, with papC (21/24, 87.5%) and sfa (16/24, 66.7%) genes being the most prevalent. Most isolates carry virulence genes primarily associated with extra-intestinal pathogenic E. coli (ExPEC) (87.5%) and enteropathogenic (EPEC) (70.8%) pathotypes. Four E. coli isolates exhibit cluster patterns. This study provides the first insight into the emergence of virulent MDR E. coli among oysters in Egypt. It underscores the potential role of oysters as a source for disseminating these strains within aquatic ecosystems, presenting a possible threat to public health.

Abstract This study aimed to isolate Streptomyces sp. from Moroccan terrestrial ecosystems and identify bioactive compounds through GC–MS analysis. Antimicrobial activity was assessed against various pathogenic microorganisms including Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 60193, and multi-drug resistant strains comprising Listeria monocytogenes, Klebsiella pneumoniae 19K 929, Proteus sp. 19K1313, Klebsiella pneumoniae 20B1572, Proteus vulgaris 16C1737, and Klebsiella pneumoniae 20B1572. Based on the results of the gene sequencing of gene 16S rRNA and phylogenetic analysis, the E2 isolate belongs to the genus Streptomyces with the highest degree of resemblance (97.51%) to the Streptomyces africanus strain NBRC 101005 (NR_112600.1). The isolate exhibited broad-spectrum antibacterial activity, with maximum efficacy against Klebsiella pneumoniae 20B1572 indicated by an inhibition zone diameter of 22.5 ± 0.71mm and a minimum inhibitory concentration (MIC) of 0.0625 mg/mL. The in vitro antioxidant potential of E2 strain was determined through screening of its ethyl acetate extract against sets of antioxidant assays. The results were indicative of E2 strain displaying strong antioxidant activity against ABTS, DPPH free radicals, and FRAP. Furthermore, there was a high significant correlation (p

Background: Indonesia is the third country with a high-rate case of tuberculosis with multi-drug resistance, for a percentage of 5% per 100.000 population. In Papua, TB-MDR becomes the main problem of health with a successful percentage of medication at 68.7%, an indicator of WHO higher than 85%. The complexity and the prolonged occurrence make the patients to have mental health illnesses, such as depression, anxiety, and stress. The field data of depression cases consisted of 65 patients. 50% with had mild depression, 20% with moderate, and 25.55 with severe. Patients with anxiety ranged from 16.7% to 37.29%. Patients with severe stress consisted of 20%. The mental illness health problems for TB-MDR patients required the roles of the nurses, such as counseling based on HOPE therapy. Purpose: Analyzed the effects of HOPE therapy to manage depression, anxiety, and stress levels. Methods: Quasi-experimental research applied a systematically assigned control group. The population consisted of patients with TB-MDR receiving medication at Jayapura's healthcare center, 40 individuals. Results: HOPE therapy effects for depression, stress, and anxiety levels applied the Wilcoxon test. The obtained result was a p-value lower than 0.05. The results indicated the effect of HOPE therapy medication on depression, stress, and anxiety levels. The intervention group had decreased depression, stress, and anxiety levels with p-values of 0.043 and 0.012. The results contradicted the control group. The obtained p-value was higher than 0.05, indicating no effect. The p-values were 0.721, 0.532, and 0.670. Conclusion: HOPE therapy was useful for TB-MDR patients with mental illness. The administered HOPE therapy for patients could improve their confidence and hopes to live better and recover.

Abstract Background Small cell lung cancer (SCLC) stands as one of the most lethal malignancies, characterized by a grim diagnosis and prognosis. The emergence of multi-drug resistance poses a significant hurdle to effective therapy. Although previous studies have implicated the long noncoding RNA LYPLAL1-DT in the tumorigenesis of SCLC, the precise role of the highly expressed LYPLAL1-DT in SCLC chemoresistance and the underlying mechanism remain inadequately understood. Methods cDDP-, VP-16- and PTX-resistant SCLC cells lines were established. The viabilities of SCLC cells were assessed by CCK-8 assay in vitro and xenograft tumor formation assay in vivo. Apoptosis was evaluated by FACS, Western blot and JC-1 fluorescence staining, while autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of LYPLAL1-DT were further investigated by gain- and loss-of-function assays in vitro. Furthermore, the therapeutic efficacy of the combination of venetoclax and HCQ with cDDP, VP-16 or PTX was evaluated by cell line, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice model. Results Our findings revealed that LYPLAL1-DT is upregulated in chemoresistant SCLC cell lines. Gain- and loss-of-function assays demonstrated that LYPLAL1-DT impairs sensitivity to cDDP, VP-16, or PTX both in vitro and in vivo. Overexpression of LYPLAL1-DT significantly enhanced autophagy and inhibited apoptosis in SCLC cells. Further analyses, including RIP and RNA pull-down assays, revealed that LYPLAL1-DT promotes the expression of BCL2 by sponging miR-204-5p and is implicated in the assembly of the autophagy-specific complex (BECN1/PtdIns3K complex). Combining venetoclax and HCQ with cDDP, VP-16, or PTX effectively mitigated chemoresistance in SCLC cells and suppressed tumor growth in CDX and PDX models without inducing obvious toxic effects. Conclusions Our findings demonstrate that upregulation of LYPLAL1-DT sequesters apoptosis through the LYPLAL1-DT/miR-204-5p/BCL2 axis and promotes autophagy by facilitating the assembly of the BECN1/PtdIns3K complex, thereby mediating multi-drug resistance of SCLC. The triple combination of venetoclax, HCQ, in conjunction with cDDP, VP-16 or PTX overcomes refractory SCLC, shedding light on a potential therapeutic target for combating SCLC chemoresistance.

Zhihong Liu,1,2,&ast; Xiaofang Liang,1,&ast; Yu Zhang,1 Wenbo Deng,1 Yulin Wang,3 Zhangping Lu,2 Qianqian Liu,2 Lianhua Wei2 1School of Public Health, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua Wei, Email 107306723@qq.comAbstract: The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.Keywords: antimicrobial resistance, multi-drug resistance, niclosamide, a derivative, drug repurposing

Background: Pseudomonas aeruginosa is a highly antimicrobial-resistant pathogen with a very narrow range of effective antibacterial agents. Therefore, finding alternative compounds is highly required, such as silver nanoparticles (AgNPs). Aim: The current study was conducted to identify the multi-drug resistance (MDR) profile and perform a phylogenetic analysis on Pseudomonas aeruginosa isolates recovered from clinical samples (human, cows, cats, and fish) and to study their susceptibility to AgNPs. Methods: 40 samples were subjected to conventional cultivation and biochemical analyses to identify P. aeruginosa. Moreover, these isolates were tested for their antibiotic resistance profile and their response to AgNPs using disk diffusion methods. PCR and Sanger-based sequencing were performed using the 16S rRNA gene as a target. Results: The results showed that all isolates were resistant to cefixime and sensitive to meropenem. Conversely, the AgNPs were effective in producing larger zones of inhibition. The PCR revealed amplification of the target, and the sequencing and phylogenetic tree of four isolates revealed close similarity with global human sequences from different regions. Conclusion: The study reveals MDR characteristics of Pseudomonas aeruginosa. The isolates are highly susceptible to silver nanoparticles. [Open Vet J 2024; 14(9.000): 2433-2440]

Objective To investigate the antibacterial effect and its preliminary mechanism of lavender essential oil on multi-drug resistant Acinetobacter baumannii. Methods Micro-dilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of lavender essential oil against multi-drug resistant Acinetobacter baumannii, and bactericidal kinetic study was employed to determine the onset and maintenance time of lavender essential oil. Meanwhile, the promoting and therapeutic effects of lavender essential oil on wound healing were observed in a mouse model of infection. Subsequently, crystal violet staining was used to determine the inhibition and clearance of multi-drug resistant Acinetobacter baumannii biofilm by lavender essential oil, and laser confocal microscopy was utilized to observe the survival of bacteria in biofilms. NanoDrop instrument was utilized to quantify the leakage of bacterial DNA nucleic acid and protein after intervention with 3 and 6 mg/mL lavender essential oil, and the leakage of bacterial potassium ion was measured by potassium ion test kit. Proteomics technology combined with bio-informatics were applied to explore the action mechanism of lavender essential oil against multi-drug resistant Acinetobacter baumannii. Results The MIC and MBC of lavender essential oil were both 6 mg/mL, which could kill almost all multi-drug resistant Acinetobacter baumannii at the time point of 120 min, and showed an obvious dose- and time-dependent manner. The overall animal model evaluation showed that both 3 and 6 mg/mL lavender essential oil could promote wound healing, and the curative effect was obvious. Further studies confirmed that 3 mg/mL lavender essential oil had a certain biofilm inhibitory effect on multi-drug resistant Acinetobacter baumannii, and 6 mg/mL also had a certain biofilm clearance effect under the same conditions. Meanwhile, when incubated at 37 ℃ for 1 h, the dose of 3 mg/mL could increase the leakage of DNA nucleic acid and protein, and significantly promote the efflux of potassium ions. Proteomic analysis suggested that the antibacterial effect of lavender essential oil may be related to affecting the oxidorereductase activity and cell metabolic process of multi-drug resistant Acinetobacter baumannii, and interfering with the biosynthesis of cell wall/membrane/envelope and other structures. Conclusion Lavender essential oil at 3 mg/mL can play an antibacterial effect against multi-drug resistant Acinetobacter baumannii, and its mechanism may be related to the destruction of bacterial biofilm and interference with bacterial metabolism.

Abstract This study addresses the distribution and antimicrobial resistance of Acinetobacter baumannii (A. baumannii) in a medical facility in Haikou City, aiming to provide essential insights for enhancing in-hospital treatment and prevention strategies. We conducted a retrospective analysis of 513 A. baumannii isolates collected from a tertiary care hospital in Haikou between January 2018 and December 2020, focusing on their antimicrobial resistance patterns. Random Amplified Polymorphic DNA (RAPD) analysis was performed on 48 randomly selected A. baumannii strains. Using Gel-pro4.0 and NTSYSspc2.10 software, we constructed dendrograms to assess the genetic diversity of these strains. Our results indicate that males between 60 and 70 years old are particularly vulnerable to A. baumannii infections, which are most frequently detected in sputum samples, with a detection rate exceeding 70%. Alarmingly, over 50% of the isolates were identified as multi-drug resistant. The RAPD-PCR fingerprinting cluster analysis demonstrated substantial genetic diversity among the strains. Using primer OPA-02 at a 45% similarity coefficient, the strains were categorized into four groups (A-D), with group A being predominant (39 strains). high-prevalence areas like the Neurosurgery and Intensive Care Medicine Wards require enhanced surveillance and targeted interventions to manage Group C infections effectively. Additionally, the varied presence of other groups necessitates customized strategies to address the specific risks in each ward. Similarly, primer 270 at a 52% similarity coefficient classified the strains into five groups (E-I), with group E being most common (36 strains). The study highlights a concerning prevalence of antimicrobial resistance, particularly multi-drug resistance, among A. baumannii strains in the Haikou hospital. The significant genetic diversity, especially within groups A and E, underscores the need for tailored hospital treatment protocols and prevention measures. These findings contribute to the growing body of research on antimicrobial resistance, emphasizing the urgent need for effective management strategies in healthcare settings.

Background: Pseudomonas aeruginosa is a key pathogen in cystic fibrosis (CF) associated infections, known for its biofilm-forming ability and resistance to multiple antibiotics. Understanding the relationship between biofilm production and antibiotic resistance profiles in clinical isolates can guide treatment strategies. Aims and Objectives: The aims of this study were to investigate the biofilm-forming abilities and antibiotic resistance profiles of clinical P. aeruginosa isolates from patients with CF and to determine the relationship between these two factors and their impact on treatment efficacy. Materials and Methods: A cross-sectional study was conducted on 100 clinical isolates of P. aeruginosa from CF patients. Biofilm-forming capacity was categorized as strong, moderate, or weak based on quantitative assays. Antibiotic resistance was assessed for ciprofloxacin, tobramycin, ceftazidime, meropenem, and piperacillin/tazobactam. Multi-drug resistance was defined as resistance to three or more antibiotic classes. Statistical correlations between biofilm-forming capacity and resistance levels were evaluated using the Chi-square tests. Results: Fifty-six percentages of isolates were strong biofilm producers, while 34% and 10% were moderate and weak producers, respectively. The highest antibiotic resistance was observed against ciprofloxacin (60%), followed by tobramycin (50%) and ceftazidime (45%). Forty percentages of the isolates were classified as multi-drug resistant. Strong biofilm producers demonstrated a significantly high correlation with antibiotic resistance (P

Background: Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB) strains. Drug-resistant TB, including mono-drug-resistant TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB), presents significant public health challenges. Methods: We conducted a systematic literature review from January 2010 to February 2024 using databases such as PubMed, Embase, Web of Science, and Google Scholar. Our focus was on empirical data related to drug resistance patterns in newly diagnosed TB cases. Non-empirical studies were excluded through meticulous filtering. For the meta-analysis, we used Review Manager (RevMan) 5.2 and assessed evidence quality using the Newcastle-Ottawa Scale (NOS). Results: Our search strategy identified 40 studies that met the inclusion criteria, encompassing a total sample size of 87,667 participants. Among new TB cases, the estimated prevalence of MDR-TB in China was 6.9% (95% CI: 5.6–8.1%). Prevalence rates for mono-drug resistance to first-line anti-TB medications were as follows: isoniazid at 18.2% (95% CI: 16.4–20.6%), rifampicin at 10.5% (95% CI: 8.6–12.8%), and ethambutol at 5.7% (95% CI: 4.1–7.3%). The prevalence of streptomycin resistance, a former first-line anti-TB drug, was 17.1% (95% CI: 14.6–19.1%). The prevalence of other types of mono-drug resistance was 15.2% (95% CI: 13.9–17.3%), and for XDR-TB, it was 0.9% (95% CI: 0.6–1.4%). Conclusions: The high prevalence of drug-resistant TB in China poses a significant public health challenge. There is an urgent need for targeted interventions and continued surveillance to combat the spread of drug-resistant TB.

Globally, there is a growing concern about Pseudomonas aeruginosa resistance to aminoglycosides. Enzymatic modification of these drugs is the predominant resistance mechanism. Additionally, P. aeruginosa possesses many efflux systems that enable it to resist a variety of antimicrobial agents. This study aimed to determine the resistance patterns to several antibiotics as well as the possible mechanisms of aminoglycosides resistance, including aminoglycosides modifying enzymes (AMEs), genes, and active efflux system, observed in clinical P. aeruginosa isolates recovered from patients admitted to Minia University Hospitals, Minia, Egypt. Isolates of P. aeruginosa were identified by traditional phenotypic tests and assessed for their in vitro susceptibility to various antibiotics. The minimum inhibitory concentrations (MICs) of some aminoglycosides were determined without and after the addition of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Aminoglycoside resistance amplified gene sequences were detected using polymerase chain reaction (PCR). Antibiotic sensitivity testing was applied on 93 clinical isolates of P. aeruginosa. The highest rate of resistance was recorded against cefepime and ceftazidime (94.6 % each), while 35.5 % of the examined strains exhibited resistance to minimally one of the evaluated aminoglycoside antibiotics. Furthermore, 49.5 % of isolates were multidrugresistant (MDR). After CCCP addition, 24.2 % of the resistant isolates restored their sensitivity to gentamicin. According to PCR analysis, aac(3)-II was the most frequently detected gene (21.2 %) followed by aph(3′)-VI (15.2 %), and aac(6’)-IIa (3 %). Multiple drug resistance was observed among P. aeruginosa strains included in this study. Resistance of P. aeruginosa to aminoglycosides is greatly influenced by efflux pumps. Coordinated measures and further investigations are urgently needed to manage aminoglycosides resistance.

Hui Ao, Huizhu Song, Jing Li Department of Pharmacy, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of ChinaCorrespondence: Jing Li, Department of Pharmacy, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299, Qingyang Road, Wuxi, Liangxi District, People’s Republic of China, Email lijingwuxi@sina.comPurpose: The increasing multi-drug resistance (MDR) is a serious threat to human health. The appropriate use of antibiotics can control the progression of MDR and clinical pharmacists play an important role in the rational use of antibiotics. There are many factors that influence the effectiveness of multi-drug resistant organisms (MDRO) infection consultations. The study aimed to establish a model to predict the outcome of consultation and explore ways to improve clinical pharmacy services.Patients and methods: Patients diagnosed with MDRO infection and consulted by clinical pharmacists were included. Univariate analysis and multivariate logistic regression analysis were used to identify independent risk factors for MDRO infection consultation effectiveness, and then a nomogram was constructed and validated.Results: 198 patients were finally included. The number of underlying diseases (OR=1.720, 95% CI: 1.260– 2.348), whether surgery was performed prior to infection (OR=8.853, 95% CI: 2.668– 29.373), ALB level (OR=0.885, 95% CI: 0.805~0.974), pharmacist title (OR=3.463, 95% CI: 1.277~9.396) and whether the recommendation was taken up (OR=0.117, 95% CI: 0.030~0.462) were identified as independent influences on the effectiveness of the consultation. The nomogram prediction model was successfully constructed and the AUC of the training set and the verification set were 0.849 (95% CI: 0.780– 0.917) and 0.761 (95% CI: 0.616– 0.907) respectively. The calibration curves exhibited good overlap between the data predicted by the model and the actual data.Conclusion: A nomogram model was developed to predict the risk of consultation failure and was shown to be good accuracy and good prediction efficiency, which can provide proactive interventions to improve outcomes for potentially treatment ineffective patients.Keywords: multi-drug resistance, nomogram, clinical pharmacist, consultation, clinical pharmacy services

Abstract Background Acinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province. Results Non-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained bla ADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite. Conclusions This study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii.

Background and Aim: Mycobacterium tuberculosis causes global concern with tuberculosis (TB). Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose additional challenges, as they resist multiple first-line drugs. This study investigated the occurrence of TB, antibiotic resistance due to inhA and katG gene mutations, and multidrug resistance in M. tuberculosis during fiscal years 2020–2022. Materials and Methods: Samples were gathered from hospitals in seven provinces of upper Southern Thailand. The study investigated the correlation between inhA and katG gene mutations in M. tuberculosis and the development of antimicrobial resistance and isoniazid resistance. Results: A total of 19,186 samples were sent to the Office of Disease Prevention and Control Region 11st, Nakhon Si Thammarat, Thailand. The results showed that 51% of the samples were obtained from patients located in Nakhon Si Thammarat, followed by Surat Thani provinces. Regarding the spatial distribution of TB-infected cases, the incidence of TB was high in the province, which has a moderate to high population density. The highest average occurrence of TB in this study was found in Phuket province (9.75/100,000 risk person-year). The detected isoniazid resistance was 394, 255, and 179 cases in 2020, 2021, and 2022, respectively. A total of 99 isolates were MDR, whereas four isolates were XDR. The antimicrobial resistance associated with the inhA mutation was 192, 142, and 105 isolates, respectively, whereas the resistance associated with the katG mutation was 249, 182, and 120 cases in 2020, 2021, and 2022, respectively. Conclusion: These findings contribute to the understanding of the occurrence of antibiotic-resistant TB that could lead to use as data for preventing MDR-TB.

Abstract Background Breast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies have been directed towards cancer cells, but these are not the unique components of the tumor bulk, where a key role is played by the tumor microenvironment (TME), whose better understanding could be crucial to obtain better outcomes. Methods We evaluated mitochondrial transfer (MT) by co-culturing Adipose stem cells with different Breast cancer cells (BCCs), through MitoTracker assay, Mitoception, confocal and immunofluorescence analyses. MT inhibitors were used to confirm the MT by Tunneling Nano Tubes (TNTs). MT effect on multi-drug resistance (MDR) was assessed using Doxorubicin assay and ABC transporter evaluation. In addition, ATP production was measured by Oxygen Consumption rates (OCR) and Immunoblot analysis. Results We found that MT occurs via Tunneling Nano Tubes (TNTs) and can be blocked by actin polymerization inhibitors. Furthermore, in hybrid co-cultures between ASCs and patient-derived organoids we found a massive MT. Breast Cancer cells (BCCs) with ASCs derived mitochondria (ADM) showed a reduced HIF-1α expression in hypoxic conditions, with an increased ATP production driving ABC transporters-mediated multi-drug resistance (MDR), linked to oxidative phosphorylation metabolism rewiring. Conclusions We provide a proof-of-concept of the occurrence of Mitochondrial Transfer (MT) from Adipose Stem Cells (ASCs) to BC models. Blocking MT from ASCs to BCCs could be a new effective therapeutic strategy for BC treatment.

Elizabethkingia meningoseptica is an uncommon nosocomial pathogen that causes meningitis, pneumonia, and sepsis in neonates and in immunocompromised individuals. It exhibits resistance to many commonly employed first-line antibiotics used to treat gram-negative pathogens. Herein, we present three cases of late-onset sepsis with multi-drug resistant (MDR) Elizabethkingia meningoseptica in high-risk neonates. Case 1 was a one-day-old preterm low-birth-weight infant who presented with respiratory distress syndrome and septic shock. The patient was intubated and administered empirical broad-spectrum antibiotics and antifungal agents. Blood culture grew Candida krusei, hence Amphotericin B was initiated. Repeat blood culture on day 27 showed gram-negative bacilli, identified as Elizabethkingia meningoseptica by MALDI-TOF . Antibiotic susceptibility testing (AST) revealed resistance to Piperacillin/Tazobactam, but sensitivity to Vancomycin, Levofloxacin, and Minocycline. IV Vancomycin was administered, which resulted in clinical improvement and negative blood culture results. Case 2 was an eleven-day-old preterm, low-birth-weight baby who presented with fever. Initial investigations revealed normal complete blood counts (CBC) parameters and elevated CRP levels. Blood and CSF cultures isolated Elizabethkingia meningoseptica with a similar AST pattern. Intravenous Ciprofloxacin was initiated with clinical improvement and negative follow-up blood cultures. Case 3 was a one-day-old preterm baby, appropriate-to-gestational age, presenting with respiratory distress syndrome. The infant was intubated and started on inotropic support and intravenous antibiotics. Blood cultures on day 4 showed Elizabethkingia meningoseptica and Vancomycin was started. Follow-up cultures on days 6 and 14 grew Acinetobacter baumannii. A combination of Levofloxacin and Colistin was added, and blood cultures were negative after seven days, with clinical improvement. Elizabethkingia meningoseptica is a significant cause of hospital-acquired infections, especially in Neonatal Intensive Care Unit (NICU), leading to outbreaks. Clinicians must have a high degree of suspicion of E. meningoseptica for gram-negative bacilli causing sepsis and meningitis in high-risk patients. Recent technological advances have enabled accurate speciation to guide therapy and reduce morbidity and mortality rates.

This study interrogates infection related data in the Burns Registry of Australia and New Zealand (BRANZ), to examine associations of multi-drug resistant organisms (MDROs) and blood stream infection (BSI). Data between July 2016 and June 2021 were analysed to determine prevalence, risk factors and outcomes associated with BSIs and MDROs: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Pseudomonas spp. (CRP), and carbapenem-resistant Enterobacter (CRE). Data completeness and value for quality improvement activity were assessed. We found a low incidence (3.4%) of the resistant organisms of interest, and no change over the study period. Fequency varied between services and increased with age and size of burn. MRSA was the commonest organism in all age groups. A positive BSI result occurred in 1.6% of patients (12.1% of cultures taken) at a median time of 10.2 days post injury. Free text identification of organisms was inconsistently documented. The low rate and patterns of acquisition of MDROs of interest and BSIs is comparable with reports from countries with low incidence of massive burns. Wider adoption of a standardized laboratory reporting framework would help realise the potential of clinical quality registries to provide data which supports evidence based infection prevention initiatives. • The registry has excellent data completeness for resistant organism items. • Overall frequency of multi-drug resistant organisms is low, but high in patients with massive burns. • Frequency of acquisition did not increase during the study. • MRSA acquisition is not associated with poorer outcomes in adults with severe burns. [ABSTRACT FROM AUTHOR]

The relationship between bacteriuria and subsequent symptomatic infections, particularly bacteraemia, has been a subject of ongoing research. We aim to investigate the clinical characteristics, long-term outcomes, and factors associated with subsequent symptomatic infection following an initial multidrug-resistant P. aeruginosa (MDRP) bacteriuria episode. A retrospective cohort study was conducted among patients with MDRP bacteriuria who were hospitalized at a tertiary care hospital from 2009 to 2018, with a 12-month follow-up period for each patient. The primary endpoint was the incidence of subsequent symptomatic MDRP infections at any site, and the secondary endpoint was the overall mortality rate. A total of 260 patients with MDRP bacteriuria were included in the analysis, of whom 155 patients (59.6%) had asymptomatic bacteriuria. Subsequent symptomatic MDRP infections were documented in 79 patients (30.3%) within 12 months of the initial bacteriuria episode: UTI (n = 47, 18.1%), pneumonia (n = 21, 8.1%), bacteraemia (n = 9, 3.5%), soft tissue infection (n = 7, 2.7%), and bone and joint infection (n = 4, 1.5%). Intensive care unit (ICU) acquisition and recurrent bacteriuria were independent risk factors of subsequent symptomatic infections in patients with MDRP bacteriuria. The overall mortality rate was 16.9%, with 31.8% of deaths estimated to be associated with MDRP infection. Solid tumours, cardiovascular diseases, chronic liver disease, chronic lung disease, ICU acquisition, absence of pyuria, and concurrent MDRP bacteraemia were independent predictors of mortality. MDRP bacteriuria has the potential for progression to symptomatic infection and associated mortality. Targeted interventions and prevention strategies were crucial to reduce subsequent infections in patients with MDRP bacteriuria, especially in high-risk patients. [ABSTRACT FROM AUTHOR]

Background: The use of plants in the treatment of microbial diseases is increasing worldwide; especially with the increase of bacterial resistance to antibiotics and the development of new diseases that have no cure in modern medicines. Aim: This research was designed to determine the antimicrobial activities of bioactive compounds isolated from Acacia nilotica (A. nilotica) against multi-drug resistant bacteria. Methods: Acacia nilotica samples (i.e., leaves, pods, and back) were collected within Aliero local government area, in Nigeria. Metabolite extraction was performed through maceration. The obtained extract was tested in vitro against multi-drug resistant bacteria that cause diarrhea: Salmonella typhimurium, S. paratyphi, Salmonella sp, Shigella dysenteriae, Shigella sp, and Shigella flexneri, using the agar well diffusion assay. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using the micro-plate serial dilution method. The synergistic (Pod + Leave Steam back) ethanolic crude extract was subjected to column and thin-layer chromatography (TLC) analyses. The obtained fractions were tested against multi-drugs resistance bacteria, and MIC and MBC of the fractions were also determined. Results: The results showed that the synergistic A. nilotica crude extract had the highest mean antibacterial activity recording inhibition zones that ranged from 15.0± 0.58 to 22.7± 0.33 mm. The MIC of ethanolic crude extracts ranged from 100 to 200 mg/ml, while the MBC ranged from 100 to > 400 mg/ ml. Conclusion: The antibacterial potential of the synergistic ethanolic fractions recorded higher activity that ranged from 16.7± 1.20 to 31.0±1.00 mm against all the tested bacteria, compared to the crude extracts. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province. Results: Non-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained blaADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite. Conclusions: This study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii. [ABSTRACT FROM AUTHOR]