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In a patient on immunosuppressant treatment, SARS-CoV-2 RNA was documented in different extra-respiratory samples over several months in the absence of positive determinations in upper respiratory samples. Whole-genome sequencing of these samples showed the acquisition of different single-nucleotide polymorphisms over time, suggesting viral evolution and thus viral viability. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae represent a common invasive infection etiological agent, whose potential carbapenem-resistance and hypermucoviscosity complicate the patient's management. Infection development often derives from gastrointestinal colonization; thus, it is fundamental to monitor asymptomatic K. pneumoniae colonization through surveillance protocols, especially for intensive care and immunocompromised patients. We described a six-month routine screening protocol from the Policlinico of Catania (Italy), while blood samples were collected from the same patients only in cases of a systemic infection suspicion. All the patients who had dissemination episodes were furtherly investigated through next-generation sequencing, analyzing both colonizing and disseminating strains. This study documents emerging invasive sequence types such as ST101, ST307, and ST395, mainly revealing blaNDM or blaKPC genes, along with siderophores and hyperproduction capsule markers as virulence factors. Most of the detected factors are presumably related to a specific plasmid content, which are extremely varied and rich. In conclusion, active surveillance through sequencing is essential to enhance awareness of local epidemiology within high-risk multi-drug resistance areas. A random sequencing analysis on the most warning microorganisms could enhance sequence typing (ST) awareness within specific settings, allowing for better prevention control strategies on their eventual persistence or diffusion. [ABSTRACT FROM AUTHOR]

Simple Summary: Wild bird species are known to be readily infected with and carry Salmonella enterica. This has two main consequences. Firstly, they may act as reservoirs in the transmission of infection to livestock species or zoonotic transmission to humans. Secondly, birds themselves may develop systemic infection, leading to high mortality disease. Recent studies have shown that specific genotypes adapted to and capable of causing disease in a range of bird species have recently evolved. Salmonella enterica is an important bacterial pathogen in humans and warm-blooded animals. Wild bird species represent both a potential reservoir for zoonotic infection and as a susceptible host to infection by host-adapted variants. Historically, wild birds were considered to be a major source of Salmonella infection in livestock, but in recent years, it has been more apparent that birds are more likely to act as a reservoir for recycling infection on farms rather than as the primary source of infection. Birds may also transmit infection to humans directly from feces or indirectly through fecal contamination of foods, including peanut butter. While many bird species can be infected with Salmonella, the rates of infection are variable, and most cases lead to intestinal carriage rather than disease. In this case, fecal shedding of Salmonella bacteria from birds can represent a risk for transmission to humans. As such, care is needed when in contact with fecal material such as that found on bird tables or feeders. In recent years, there have been emergences of Salmonella Typhimurium genotypes associated with high mortality in songbirds or passerine birds, resulting in 'die offs' in Europe, Israel, New Zealand and the US. Additionally, S. typhimurium DT2 and other variant Copenhagen genotypes are associated with high mortality disease in pigeons. These genotypes show evidence of evolution towards adaptation to specific hosts, with pseudogenes leading to loss of functional metabolic pathways and specific virulence factors. These 'signatures of adaptation' are common in host-adapted Salmonella serovars and suggest these S. typhimurium isolates are evolving to adapt to specific avian hosts. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Protothecosis in dogs is a rare, yet emerging disease, distinguished by its often‐aggressive clinical course and high fatality rate. Our study was conducted to enhance treatment protocols for affected dogs by better understanding the genetic diversity and drug resistance patterns of Prototheca species.To identify species and drug susceptibility profiles of an international collection of 28 Prototheca strains isolated from cases of protothecosis in dogs.None.Retrospective study. Species‐level identification was made for isolates from 28 dogs in 6 countries by molecular typing with the partial cytb gene as a marker. For the determination of minimum inhibitory concentrations (MICs) and minimum algicidal concentrations (MACs), the Clinical Laboratory Standards Institute (CLSI) protocol (M27‐A3) was used.Prototheca bovis was the most prevalent species, accounting for 75% (21/28) of the cases, followed by P. wickerhamii (18%; 5/28) and P. ciferrii (7%; 2/28). Of the 6 drugs tested, efinaconazole (EFZ) was the most potent in vitro, with its median MIC and MAC values equal to 0.125 mg/L. The lowest activity was found for fluconazole (FLU), with MIC and MAC medians of 48 mg/L and 64 mg/L, respectively.Our study identifies P. bovis as the species that most frequently causes protothecosis in dogs, which suggests the possibility of cross‐species infection from other animals, especially cows. Additionally, it indicates that EFZ could be used in the treatment of infection in the colon. [ABSTRACT FROM AUTHOR]

Streptococcus species are important pathogens implicated in bovine mastitis, causing considerable economic losses within the global dairy industry. With the development of multidrug-resistant bacteria, it is crucial to develop novel antibiotic alternatives. Here, we constructed a novel chimeric endolysin, Cly2v, which comprises the Ply2741 CHAP domain (1-155aa) and the PlyV12 CBD domain (146-314aa). Biochemical characterization analysis indicated that Cly2v exhibits a melting temperature of 50.7°C and retains stable bactericidal activity at pH = 3-10. In vitro experiments demonstrated that Cly2v exhibited more efficient bactericidal activity against Streptococcus compared to the parental endolysin Ply2741. Cly2v (25 µg/mL) can effectively inhibit and reduce biofilms formed by Streptococcus, resulting in a 68 and 44% reduction in OD590nm for S. agalactiae X2 and S. uberis 002-1 biofilms. Notably, in a mouse mastitis model, treatment with Cly2v (50 µg/gland) led to a reduction in bacterial load by 2.16 log10CFU/ml and decreased inflammatory cytokine levels in mammary tissue. To our knowledge, this represents the first application of a chimeric endolysin in the treatment of early-stage mouse mastitis induced by streptococci. Additionally, in a systemic infection model, treatment with Cly2v (400 µg/mouse) provided protection rates of up to 100 and 78% against S. agalactiae ATCC13813 infections when challenged for 1 h and 3 h, respectively. Furthermore, a significant reduction in bacterial loads was observed in the blood and organs compared to the PBS group. In summary, Cly2v possesses significant potential as an alternative antibiotic for the treatment of streptococci-induced bovine mastitis and systemic infections. [ABSTRACT FROM AUTHOR]

Fungal infections are a significant cause of systemic infections in immunosuppressed patients. Studies indicate that the most prevalent fungal pathogens include Candida albicans (25 %), non-albicans Candida species (25 %), and Aspergillus species (25 %) [1]. Malassezia, a lipophilic, opportunistic pathogenic yeast, primarily causes skin infections, but there are increasing reports of invasive infections. This report describes a Suspected systemic multisystem infection with Malassezia in a bone marrow transplant patient, detailing the diagnosis and treatment process. The article also discusses the identification methods of Malassezia and the role of antifungal drugs.

ABSTRACT Murine models are commonly used to understand pathogen and host determinants of systemic infection. While these models have proven beneficial for uncovering bacterial mechanisms required for progression to invasive disease, it can be challenging to draw comparisons across studies as several different routes of infection are standardly used for these experiments. In this study, one of the leading bacterial meningeal pathogens, Streptococcus agalactiae, or Group B Streptococcus (GBS), was used to compare experimental outcomes of two commonly used routes of hematogenous infection, lateral tail vein injection and retro-orbital venous sinus injection. Here we demonstrate that both routes of infection result in systemic disease and the onset of clinical symptoms of infection. We show that retro-orbital venous sinus injection results in an initial increase in bacterial dissemination to the spleen and brain tissue of GBS-infected mice, while an increased bacterial burden was only detected in brain tissues at a later time point. Despite differences in initial dissemination and brain bacterial burden, we found that the route of infection did not significantly impact bacterial burden in the blood, kidney, spleen, heart, and lung tissues at experimental endpoints; and similarly did not impact animal health scores during infection; cytokine and proinflammatory protein abundance in the brain tissue; or overall animal survival. In summary, these findings suggest that both tail vein injection and retro-orbital venous sinus injection are viable models to study Group B streptococcal systemic infection and result in largely similar disease outcomes within our tested parameters.IMPORTANCEStreptococcus agalactiae or Group B Streptococcus (GBS) is the leading cause of invasive disease in neonates and immunocompromised adults and is implicated in severe cases of sepsis, pneumonia, and meningitis. Established murine models of hematogenous systemic infection allow for better understanding and investigation of bacterial dispersion, pathogenesis, meningeal inflammation, and interaction with the host. Here we compared two routes of infection, intravenous lateral tail vein and retro-orbital venous sinus, demonstrating that similar experimental outcomes can be observed, regardless of the route of infection for GBS, specifically. These findings help to reinforce the utility of different systemic infection models and provide insight into comparisons across different established models and how these models can be applied in microbial research.

Abstract Growing evidence has implicated systemic infection as a significant risk factor for the development and advancement of Alzheimer’s disease (AD). With the emergence of SARS-CoV-2 (COVID-19) and the resultant pandemic, many individuals from the same aging population vulnerable to AD suffered a severe systemic infection with potentially unidentified long-term consequences for survivors. To study the impact of COVID-19 survival on the brain’s intrinsic immune system in a population also suffering from AD, we profiled post-mortem brain tissue from patients in the UF Neuromedicine Human Brain and Tissue Bank with a diagnosis of AD who survived a COVID-19 infection (COVID-AD) and contrasted our findings with AD patients who did not experience a COVID-19 infection, including a group of brain donors who passed away before arrival of SARS-CoV-2 in the United States. We assessed disease-relevant protein pathology and microglial and astrocytic markers by quantitative immunohistochemistry and supplemented these data with whole tissue gene expression analysis performed on the NanoString nCounter® platform. COVID-AD patients showed slightly elevated Aβ burden in the entorhinal, fusiform, and inferior temporal cortices compared to non-COVID-AD patients, while tau pathology burden did not differ between groups. Analysis of microglia revealed a significant loss of microglial homeostasis as well as exacerbated microgliosis in COVID-AD patients compared to non-COVID-AD patients in a brain region-dependent manner. Furthermore, COVID-AD patients showed reduced cortical astrocyte numbers, independent of functional subtype. Transcriptomic analysis supported these histological findings and, in addition, identified a dysregulation of oligodendrocyte and myelination pathways in the hippocampus of COVID-AD patients. In summary, our data demonstrate a profound impact of COVID-19 infection on neuroimmune and glial pathways in AD patients persisting for months post-infection, highlighting the importance of peripheral to central neuroimmune crosstalk in neurodegenerative diseases.

Highlight: Hyponatremia is a potentially life-threatening condition. Refracter hyponatremia can be seen in patients with systemic infection who have undergone therapy. ABSTRACT Introduction: Hyponatremia is a condition in which the sodium serum level is below the normal range. This condition is most common in hospitalized patients receiving systemic infection therapy and can lead to worse outcomes, potentially life-threatening.Objective: This study aimed to summarize the incidence of refractory hyponatremia due to systemic infection therapy. Methods: This was a systematic literature search conducted in October 2023 on the online database PubMed regarding refractory hyponatremia due to systemic. The analysis excluded narrative reviews, non-English studies, and studies that only discussed transient hyponatremia or local infections. Results: A total of 10 case reports of 11 patients were included in the final analysis. The mean age of patients was 46.63 years (SD = 20.79 years), and 63.64% were male. Strongloides stercoralis hyperinfection was the most common cause of systemic infection (54%). It was followed by disseminated Varicella-zoster virus infection (28%), tuberculosis (9%), and systemic nocardiosis (9%). The most common cause of immune compromise is stem cell transplant recipients (28%), followed by miliary tuberculosis (18%). Up to 91% of cases are caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which is the pathophysiology of hyponatremia. Conclusion: Most patients with systemic infections and refractory hyponatremia have conditions that encourage immune compromise. The treatment of systemic infections is a priority since they contribute to hyponatremia.

Background: The lactate/pyruvate (LP) ratio has been studied as an alternative to serum lactate to determine clinical prognosis. Despite its clinical utility, there is a paucity of evidence evaluating the role of the L/P ratio in patients with sepsis. Methods: We assessed the clinical utility of the L/P ratio in patients with sepsis. The L/P ratio was measured at baseline, 4 and 8 h after admission. Our primary outcome was to determine the prognostic utility of the L/P ratio on the 15-day mortality risk. Our secondary outcomes were to compare the L/P ratio across time and its prognostic utility against standard risk calculators such as APACHE-II and SOFA scores. Results: We had a total of 80 patients, with 18 (22.5%) survivors and 62 (77.5%) non-survivors. While we found that patients having higher L/P ratios at 8 h had an increased 30-mortality risk (OR 1.08, 95% CI 1.02–1.18), the model's performance showed no difference when compared to other measurements of the L/P ratio that showed no association with mortality (p-value: 0.45). For our secondary outcome, we found that the APACHE-II and SOFA scores have better performance and predictability than the L/P ratio (AUC 0.83 and AUC 0.80, respectively), but showed no association with mortality (OR 1.07, 95% CI 1.01–1.17 and OR 1.08, 95% CI 1.02–1.18). Conclusions: Based on our findings, the L/P ratio appears to function more effectively as an early predictor of mortality when used as an adjuvant biomarker with other clinical parameters. [ABSTRACT FROM AUTHOR]

Growing evidence has implicated systemic infection as a significant risk factor for the development and advancement of Alzheimer's disease (AD). With the emergence of SARS-CoV-2 (COVID-19) and the resultant pandemic, many individuals from the same aging population vulnerable to AD suffered a severe systemic infection with potentially unidentified long-term consequences for survivors. To study the impact of COVID-19 survival on the brain's intrinsic immune system in a population also suffering from AD, we profiled post-mortem brain tissue from patients in the UF Neuromedicine Human Brain and Tissue Bank with a diagnosis of AD who survived a COVID-19 infection (COVID-AD) and contrasted our findings with AD patients who did not experience a COVID-19 infection, including a group of brain donors who passed away before arrival of SARS-CoV-2 in the United States. We assessed disease-relevant protein pathology and microglial and astrocytic markers by quantitative immunohistochemistry and supplemented these data with whole tissue gene expression analysis performed on the NanoString nCounter® platform. COVID-AD patients showed slightly elevated Aβ burden in the entorhinal, fusiform, and inferior temporal cortices compared to non-COVID-AD patients, while tau pathology burden did not differ between groups. Analysis of microglia revealed a significant loss of microglial homeostasis as well as exacerbated microgliosis in COVID-AD patients compared to non-COVID-AD patients in a brain region-dependent manner. Furthermore, COVID-AD patients showed reduced cortical astrocyte numbers, independent of functional subtype. Transcriptomic analysis supported these histological findings and, in addition, identified a dysregulation of oligodendrocyte and myelination pathways in the hippocampus of COVID-AD patients. In summary, our data demonstrate a profound impact of COVID-19 infection on neuroimmune and glial pathways in AD patients persisting for months post-infection, highlighting the importance of peripheral to central neuroimmune crosstalk in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Europe has suffered unprecedented epizootics of high pathogenicity avian influenza (HPAI) clade 2.3.4.4b H5N1 since Autumn 2021. As well as impacting upon commercial and wild avian species, the virus has also infected mammalian species more than ever observed previously. Mammalian species involved in spill over events have primarily been scavenging terrestrial carnivores and farmed mammalian species although marine mammals have also been affected. Alongside reports of detections of mammalian species found dead through different surveillance schemes, several mass mortality events have been reported in farmed and wild animals. In November 2022, an unusual mortality event was reported in captive bush dogs (Speothos venaticus) with clade 2.3.4.4b H5N1 HPAIV of avian origin being the causative agent. The event involved an enclosure of 15 bush dogs, 10 of which succumbed during a nine-day period with some dogs exhibiting neurological disease. Ingestion of infected meat is proposed as the most likely infection route.

Klebsiella pneumoniae represent a common invasive infection etiological agent, whose potential carbapenem-resistance and hypermucoviscosity complicate the patient’s management. Infection development often derives from gastrointestinal colonization; thus, it is fundamental to monitor asymptomatic K. pneumoniae colonization through surveillance protocols, especially for intensive care and immunocompromised patients. We described a six-month routine screening protocol from the Policlinico of Catania (Italy), while blood samples were collected from the same patients only in cases of a systemic infection suspicion. All the patients who had dissemination episodes were furtherly investigated through next-generation sequencing, analyzing both colonizing and disseminating strains. This study documents emerging invasive sequence types such as ST101, ST307, and ST395, mainly revealing blaNDM or blaKPC genes, along with siderophores and hyperproduction capsule markers as virulence factors. Most of the detected factors are presumably related to a specific plasmid content, which are extremely varied and rich. In conclusion, active surveillance through sequencing is essential to enhance awareness of local epidemiology within high-risk multi-drug resistance areas. A random sequencing analysis on the most warning microorganisms could enhance sequence typing (ST) awareness within specific settings, allowing for better prevention control strategies on their eventual persistence or diffusion.

Salmonella enterica serovar Gallinarum (S. gallinarum) is an important host-specific pathogen that causes fowl typhoid, a severe systemic, septicemic, and fatal infection, in chickens. S. gallinarum causes high morbidity and mortality in chickens and poses a significant burden and economic losses to the poultry industry in many developing countries. However, the virulence factors and mechanisms of S. gallinarum-induced systemic infection in chickens remain poorly understood. In this study, we constructed a Salmonella pathogenicity island-14 (SPI-14) mutant strain (mSPI-14) of S. gallinarum and evaluated the pathogenicity of mSPI-14 in the chicken systemic infection model. The mSPI-14 exhibited the same level of bacterial growth and morphological characteristics but significantly reduced resistance to bile acids compared with the wild-type (WT) strain in vitro. The virulence of mSPI-14 was significantly attenuated in the chicken oral infection model in vivo. Chickens infected with WT showed typical clinical symptoms of fowl typhoid, with all birds succumbing to the infection within 6 to 9 days post-inoculation, and substantial increases in bacterial counts and significant pathological changes in the liver and spleen were observed. In contrast, all mSPI-14-infected chickens survived, the bacterial counts in the organs were significantly lower, and no significant pathological changes were observed in the liver and spleen. The expression of interleukin (IL)-1β, IL-12, CXCLi1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the liver of mSPI-14-infected chickens were significantly lower than those in the WT-infected chickens. These results indicate that SPI-14 is a crucial virulence factor in systemic infection of chickens, and avirulent mSPI-14 could be used to develop a new attenuated live vaccine to prevent S. gallinarum infection in chickens. [ABSTRACT FROM AUTHOR]

The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice's survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies. [ABSTRACT FROM AUTHOR]

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a formidable pathogen, causing severe infections in humans and animals, often leading to local and systemic inflammation. In light of this, it becomes imperative to explore novel therapeutic avenues. One such promising approach is the utilization of herbal-derived antioxidants, with katuk leaves (Sauropus androgynus) being a prime example. This study aimed to evaluate the efficacy of katuk leaves alcoholic extract (KLE) against systemic MRSA infection in rat models. Materials and methods: This study used 36 male Sprague-Dawley rats. They were divided into six groups including, healthy rats (Group C), infected rats without treatment (Group K), infected rats + 100 mg vancomycin per kg BW (Group V), infected rats + 1,000 mg/kg BW of KLE (Group T1), infected rats + 2,000 mg/kg BW of KLE (Group T2), and infected rats + 4,000 mg/kg BW of KLE (Group T4). The therapy was given twice daily for seven days. On the final day, the blood and sera were collected and tested against total erythrocytes, leucocytes, indices of erythrocytes, differential leucocyte count, and C-reactive protein (CRP). Results: The findings showed that the administration of 4,000 mg/kg BW of KLE potentially leads to more favorable changes in haematological parameters compared to the healthy group, particularly for hemoglobin (Hb), packed cell volume (PCV), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), platelets, monocytes, neutrophils, and CRP. Additionally, the 4,000 mg/kg BW of KLE increases the ratio of lymphocytes/neutrophils compared to the other groups. Conclusion: The KLE has the critical benefit of being a systemic antibacterial agent against MRSA at dosage 4,000 mg/kg BW, especially in improving the haematological profile and CRP in rat models. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of a systemic lipopolysaccharide (LPS) stimulus in the course of laser-induced choroidal neovascularization (CNV) in C57BL/6 J mice. A group of CNV-subjected mice received 1 mg/kg LPS via the tail vein immediately after CNV induction. Mouse eyes were monitored in vivo with fluorescein angiography for 2 weeks. In situ hybridization and flow cytometry were performed in the retina at different time points. LPS led to increased fluorescein leakage 3 days after CNV, correlated with a large influx of monocyte-derived macrophages and increase of pro-inflammatory microglia/macrophages in the retina. Additionally, LPS enhanced Vegfα mRNA expression by Glul-expressing cells but not Aif1 positive microglia/macrophages in the laser lesion. These findings suggest that systemic LPS exposure has transient detrimental effects in the course of CNV through activation of microglia/macrophages to a pro-inflammatory phenotype and supports the important role of these cells in the CNV course. [ABSTRACT FROM AUTHOR]

Drug-resistant microbes typically carry mutations in genes involved in critical cellular functions and may therefore be less fit under drug-free conditions than susceptible strains. Candida glabrata is a prevalent opportunistic yeast pathogen with a high rate of fluconazole resistance (FLZR), echinocandin resistance (ECR), and multidrug resistance (MDR) relative to other Candida. However, the fitness of C. glabrata MDR isolates, particularly in the host, is poorly characterized, and studies of FLZR isolate fitness have produced contradictory findings. Two important host niches for C. glabrata are macrophages, in which it survives and proliferates, and the gut. Herein, we used a collection of clinical and lab-derived C. glabrata isolates to show that FLZR C. glabrata isolates are less fit inside macrophages than susceptible isolates and that this fitness cost is reversed by acquiring ECR mutations. Interestingly, dual-RNAseq revealed that macrophages infected with drug-resistant isolates mount an inflammatory response whereas intracellular drug-resistant cells downregulate processes required for in-host adaptation. Furthermore, drug-resistant isolates were outcompeted by their susceptible counterparts during gut colonization and in infected kidneys, while showing comparable fitness in the spleen. Collectively, our study shows that macrophage-rich organs, such as the spleen, favor the retention of MDR isolates of C. glabrata. [ABSTRACT FROM AUTHOR]

Objective: This article describes a case of polymicrobial Arcanobacterium haemolyticum pharyngitis and sinusitis complicated by intracranial complications and reviews similar cases in the literature Case summary: A 21-year-old immunocompetent male presented with symptoms of sore throat, rhinorrhoea, lethargy, headache, and rash. Imaging demonstrated sinusitis, pre-septal sinusitis, peritonsillar abscess formation, subdural empyema and cerebritis. He was managed with endoscopic sinus surgery, craniotomy for evacuation of subdural empyema and antibiotics. Microbiological samples demonstrated growth of A. haemolyticum, strep. anginosus, and fusobacterium necrophorum. He subsequently developed a cerebral abscess requiring stereotactic needle drainage. After a prolonged course of antibiotics, the patient was discharge and made a good recovery. Discussion: A. haemolyticum is an uncommon cause of non-streptococcal pharyngitis that may occur alongside other microorganisms and is rarely associated with severe intracranial complications. This organism and its antibiotic susceptibility patterns should be considered in complicated upper respiratory tract infections in immunocompetent hosts. Penicillins and macrolide antibiotics form the mainstay of therapy for A. haemolyticum.

Systemic infections can yield distinct outcomes in different tissues. In mice, intravenous inoculation of Escherichia coli leads to bacterial replication within liver abscesses, while other organs such as the spleen clear the pathogen. Abscesses are macroscopic necrotic regions that comprise the vast majority of the bacterial burden in the animal, yet little is known about the processes underlying their formation. Here, we characterize E. coli liver abscesses and identify host determinants of abscess susceptibility. Spatial transcriptomics revealed that liver abscesses are associated with heterogenous immune cell clusters comprised of macrophages, neutrophils, dendritic cells, innate lymphoid cells, and T-cells that surround necrotic regions of the liver. Abscess susceptibility is heightened in the C57BL lineage, particularly in C57BL/6N females. Backcross analyses demonstrated that abscess susceptibility is a polygenic trait inherited in a sex-dependent manner without direct linkage to sex chromosomes. As early as 1 d post infection, the magnitude of E. coli replication in the liver distinguishes abscess-susceptible and abscess-resistant strains of mice, suggesting that the immune pathways that regulate abscess formation are induced within hours. We characterized the early hepatic response with single-cell RNA sequencing and found that mice with reduced activation of early inflammatory responses, such as those lacking the LPS receptor TLR4 (Toll-like receptor 4), are resistant to abscess formation. Experiments with barcoded E. coli revealed that TLR4 mediates a tradeoff between abscess formation and bacterial clearance. Together, our findings define hallmarks of E. coli liver abscess formation and suggest that hyperactivation of the hepatic innate immune response drives liver abscess susceptibility. [ABSTRACT FROM AUTHOR]

Aims Infections resulting from cardiac implantable electronic device (CIED) implantation are severely impacting on patients' and on health care systems. The use of TYRXTM absorbable antibiotic-eluting envelope has proven to decrease major CIED infections within 12 months of CIED surgery. The aim is to evaluate the impact of the envelope use on infection-related clinical events in a real-world contemporary patient population. Methods and results Data on patients undergoing CIED surgery were collected prospectively by participating centers of the One Hospital ClinicalService project. Patients were divided into two groups according to whether TYRXTM absorbable antibiotic-eluting envelope was used or not. Out of 1819 patients, 872 (47.9%) were implanted with an absorbable antibiotic-eluting envelope and included in the Envelope group and 947 (52.1%) patients who did not receive an envelope were included in the Control group. Compared to control, patients in the Envelope group had higher thrombo-embolic or hemorrhagic risk, higher BMI, lower LVEF and more comorbidities. During a mean follow-up of 1.4 years, the incidence of infection-related events was significantly higher in the control compared to the Envelope group (2.4% vs. 0.8%, P = 0.007). The five-year cumulative incidence of infection-related events was 8.1% in the control and 2.1% in the Envelope group (HR: 0.34, 95%CI: 0.14–0.80, P = 0.010). Conclusion In our analysis, the use of an absorbable antibiotic-eluting envelope in the general CIED population was associated with a lower risk of systemic and pocket infection. [ABSTRACT FROM AUTHOR]

Background: Dermatophytosis is one of the most common fungal infections worldwide. The distribution of dermatophytes varies across continents, but the genera Trichophyton and Microsporum have emerged as the main isolated agents in humans and animals. Objectives: To validate Drosophila melanogaster flies as a fast and feasible model to study dermatophytic infections. Methods: Wild‐type (WT) and Toll‐deficient D. melanogaster flies were infected by Trichophyton rubrum, T. mentagrophytes, Microsporum canis and Nannizzia gypsea by pricking with a needle previously dipped in inoculum concentrations ranging from 103 to 108 colony‐forming units/mL. Establishment of infection was confirmed by survival curves, histopathological analysis and fungal burden. Thereafter, flies were treated with terbinafine, itraconazole and clioquinol. Results: WT flies were predominantly resistant to the infection, whereas Toll‐deficient flies succumbed to the four dermatophyte genera tested. The antifungal drugs protected flies from the infection, except for N. gypsea whose survival curves did not differ from the untreated group. Conclusions: This pilot study confirms that D. melanogaster is a suitable model to study the virulence and antifungal drug efficacy in dermatophyte species. [ABSTRACT FROM AUTHOR]

Yonathan Aliye Asfaw,1,2 Helen Huang,2,3 Muhammad Taimur,2,4 Ayush Anand,2,5 Sujan Poudel,2 Tulika Garg,2,6 Bethlehem Aliye Asfaw,1,2 Befekadu Molalegn Abebe,1,2 Hanieh Akbariromani,2,7 Gavrilo Lazovic,8 Wilson Cueva9 1Internal Medicine Department, University of Gondar, College of Medicine and Health Sciences, Gondar, Ethiopia; 2Department of Research & Academic Affairs, Larkin Community Hospital, South Miami, FL, USA; 3Internal Medicine Department, University of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; 4Internal Medicine Department, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan; 5Internal Medicine Department, B. P. Koirala Institute of Health Sciences, Dharan, Nepal; 6Internal Medicine Department, Government Medical College and Hospital, Chandigarh, India; 7Internal Medicine Department, Islamic Azad University, Tehran Medical Branch, Tehran, Iran; 8Department of Emergency Medicine, Larkin Community Hospital, South Miami, FL, USA; 9Department of Neurology, Larkin Community Hospital, South Miami, FL, USACorrespondence: Yonathan Aliye Asfaw, Internal Medicine Department, University of Gondar, College of Medicine and Health Sciences, Gondar, Ethiopia, Email dreaminglatee@gmail.comAbstract: Cerebral venous thrombosis (CVT) is a cerebrovascular disorder caused by complete or partial occlusion of the cerebral venous and sinus system. The etiology has been attributed to hypercoagulability and pro-thrombotic states, leading to raised intracranial pressures that often manifest as headaches and focal neurological deficits. However, the multifactorial nature of CVT can create a diagnostic conundrum for clinicians. We describe a unique case of a 16-year-old female who presented with convulsions, postictal confusion, and drowsiness followed by residual weakness of her extremities. She initially presented to the primary care center with headache, high-grade fever, and altered mental status and was empirically treated for pyogenic meningitis. The patient failed to improve with a week of antibiotics and was referred to the tertiary care center for urgent attention. On presentation, the patient developed VI and VII cranial nerve palsy. Subsequently, MRI images showed filling defects in the superior sagittal, right transverse, and sigmoid sinuses with right parietal gyral T1 hyperintensity and T2 hypo-intensity. She was diagnosed with septic CVT based on sinus venous thrombosis and venous infarction, probably secondary to meningococcal pneumonia. It can be challenging to distinguish between both conditions as their presentations overlap. Moreover, cranial nerve palsy is an infrequent manifestation of CVT, with unclear pathogenesis. We highlight the role of neuro-imaging in the early detection of CVT and bring to light the unfamiliar symptoms and a more varied clinical spectrum that may hinder the diagnosis in a limited-resource setting. Future research should be explicitly modeled to improve the diagnostic efficiency of CVT and improve outcomes in younger patient populations.Keywords: cerebral venous thrombosis, meningitis, cranial nerve palsy, systemic infection, neuro-imaging, case report

ABSTRACT The emergence of Brucella infections in marine mammals is a growing concern. The present study reports two cases of systemic Brucella pinnipedialis infection detected in bottlenose dolphins (Tursiops truncatus) pair stranded together in the Cantabrian coast of Spain. Both animals showed systemic lesions associated with the Brucella infection, more severe in the younger dolphin, considered the likely offspring of the other individual. Real-time PCR, bacterial culture, and whole-genome sequencing were used to detect and characterize the Brucella strains involved in both dolphins. The phylogenetic analysis performed on the Brucella genomes retrieved revealed that the species involved was B. pinnipedialis (ST25). Both animals resulted seropositive in a commercial multispecies blocking ELISA but tested negative in the standard Rose Bengal test. To the best of our knowledge, this is the first report of a systemic infection resulting in various lesions associated with Brucella pinnipedialis (ST25) in two bottlenose dolphins. It is also the initial isolation of Brucella in the milk of a non-pregnant or non-aborting female cetacean likely stranded with its offspring. These findings provide new insights into the epidemiology and clinical impact of B. pinnipedialis infection in cetaceans and underscore the importance of continued diagnostic surveillance to gain better understanding of brucellosis effects and transmission in marine mammal populations. IMPORTANCE Brucella spp. are zoonotic pathogens that can affect both terrestrial and marine mammals. Brucella ceti has been identified in various cetacean species, but only one sequence type (ST27) has been reported in humans. However, it is important to conduct surveillance studies to better understand the impact of marine Brucella species on marine mammals, a typically understudied host group. Here, we describe a systemic infection by two related strains of Brucella pinnipedialis (ST25) in a couple of live-stranded bottlenose dolphins, with more severe lesions in the younger animal. Furthermore, B. pinnipedialis was first detected in milk from a female cetacean that stranded with its offspring. Our study reveals novel insights into the epidemiology and pathological consequences of B. pinnipedialis infections in cetaceans, emphasizing the crucial importance of ongoing surveillance and accurate diagnosis to understand the impact of this pathogen on marine mammal populations.

ABSTRACTStreptococcus pyogenes (group A streptococcus; GAS) causes a variety of invasive diseases (iGAS) such as bacteremia, toxic shock syndrome, and pneumonia, which are associated with high mortality despite the susceptibility of the bacteria to penicillin ex vivo. Epidemiologic studies indicate that respiratory influenza virus infection is associated with an increase in the frequency of iGAS diseases, including those not directly involving the lung. We modified a murine model of influenza A (IAV)-GAS superinfection to determine if viral pneumonia increased the susceptibility of mice subsequently infected with GAS in the peritoneum. The results showed that respiratory IAV infection increased the morbidity (weight loss) of mice infected intraperitoneally (i.p.) with GAS 3, 5, and 10 d after the initial viral infection. Mortality was also significantly increased when mice were infected with GAS 3 and 5 d after pulmonary IAV infection. Increased mortality among mice infected with virus 5 d prior to bacterial infection correlated with increased dissemination of GAS from the peritoneum to the blood, spleen, and lungs. The interval was also associated with a significant increase in the pro-inflammatory cytokines IFN-γ, IL-12, TNF-α, MCP-1 and IL-27 in sera. We conclude, using a murine model, that respiratory influenza virus infection increases the likelihood and severity of systemic iGAS disease, even when GAS infection does not originate in the respiratory tract.

To cause infection, pathogens must overcome bottlenecks imposed by the host immune system. These bottlenecks restrict the inoculum and largely determine whether pathogen exposure results in disease. Infection bottlenecks therefore quantify the effectiveness of immune barriers. Here, using a model of Escherichia coli systemic infection, we identify bottlenecks that tighten or widen with higher inoculum sizes, revealing that the efficacy of innate immune responses can increase or decrease with pathogen dose. We term this concept "dose scaling". During E. coli systemic infection, dose scaling is tissue specific, dependent on the lipopolysaccharide (LPS) receptor TLR4, and can be recapitulated by mimicking high doses with killed bacteria. Scaling therefore depends on sensing of pathogen molecules rather than interactions between the host and live bacteria. We propose that dose scaling quantitatively links innate immunity with infection bottlenecks and is a valuable framework for understanding how the inoculum size governs the outcome of pathogen exposure. [ABSTRACT FROM AUTHOR]

Clinical signs in 4 cases of salmonellosis in cats included vomiting, diarrhea (2 cases each), fever, dystocia, icterus, and seizures (1 case each). Three cats died, and one was euthanized. Grossly, all cats were in poor body condition and had yellow-to-dark-red perianal feces (3 cases), oral and ocular pallor (2 cases) or icterus (1 case), fluid or pasty yellow intestinal contents (4 cases), white or dark-red-to-black depressed areas on the hepatic surface (2 cases), yellow abdominal fluid with swollen abdominal lymph nodes (1 case), and fibrin strands on the placental chorionic surface (1 case). Histologically, all cats had necrotizing enterocolitis and random hepatocellular necrosis. Other histologic findings included mesenteric (4 cases) or splenic (2 cases) lymphoid necrosis, and endometrial and chorioallantoic necrosis (1 case). Gram-negative bacilli were observed within neutrophils and macrophages in the intestinal lamina propria (4 cases), liver, spleen, lymph node, endometrium, and placenta (1 case each). Aerobic bacterial culture on frozen samples of small intestine, mesenteric lymph node, lung, and liver yielded Salmonella enterica subsp. enterica. Serotyping was consistent with S. Enteritidis (cases 1, 3) and S. Typhimurium (cases 2, 4). [ABSTRACT FROM AUTHOR]

Introduction: Candida albicans is a commensal fungus that colonizes most healthy individuals' skin and mucosal surfaces but can also cause life-threatening invasive infections, particularly in immunocompromised patients. Despite antifungal treatment availability, drug resistance is increasing, and mortality rates remain unacceptably high. Heat shock protein Ssa1, a conserved member of the Hsp70 family in yeast, is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and enables C. albicans to cause maximal damage to host cells and induces disseminated and oropharyngeal disease. Result: Here we discovered a mouse monoclonal antibody (mAb 13F4) that targeting C. albicans Ssa1 with high affinity (EC50 = 39.78 ng/mL). mAb 13F4 prevented C. albicans from adhering to and invading human epithelial cells, displayed antifungal activity, and synergized with fluconazole in proof of concept in vivo studies. mAb 13F4 significantly prolonged the survival rate of the hematogenous disseminated candidiasis mice to 75%. We constructed a mAb 13F4 three-dimensional structure using homology modeling methods and found that the antigen-binding fragment (Fab) interacts with the Ssa1 N-terminus. Discussion: These results suggest that blocking Ssa1 cell surface function may effectively control invasive C. albicans infections and provide a potential new treatment strategy for invasive fungal infections. [ABSTRACT FROM AUTHOR]

Background: The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series. Objectives: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease. Methods: We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non‐CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi‐squared test was used to compare mortality between pairs of antifungal drugs. Results: We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3–71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49–61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14–61), meningitis (29/185, 14%, 95%CI: 7–25), hydrocephalus (41/185, 37%, 95%CI: 7–83) and vasculitis (18/185, 6%, 95%CI: 1–22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole. Conclusion: Central nervous system histoplasmosis usually presents subacute‐to‐chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality. [ABSTRACT FROM AUTHOR]

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The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice’s survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.

Group A Streptococcus (GAS) is a human-specific pathogen that evades the host immune response through the elaboration of multiple virulence factors. Although many of these factors have been studied, numerous proteins encoded by the GAS genome are of unknown function. Herein, we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function-annotated subsequently as S protein-in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulence in vitro and in vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants. In vivo, the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory.

Sepsis is defined as organ failure caused by dysregulated host response to infection. While early antibiotic treatment in patients with acute infection is essential, treating non-infectious patients must be avoided. Current guidelines recommend procalcitonin (PCT) to guide discontinuation of antibiotic treatment. For initiation of therapy, there is currently no recommended biomarker. In this study, we evaluated Host-Derived Delta-like Canonical Notch Ligand 1 (DLL1), a monocyte membrane ligand that has shown promising results in differentiating infectious from non-infectious critically ill patients. Soluble DLL1 levels were measured in plasma samples of six different cohorts. The six cohorts comprise two cohorts with non-infectious inflammatory auto-immune diseases (Hidradenitis Suppurativa, Inflammatory Bowel Disease), one cohort of bacterial skin infection, and three cohorts of suspected systemic infection or sepsis. In total, soluble DLL1 plasma levels of 405 patients were analyzed. Patients were divided into three groups: inflammatory disease, infection, and sepsis (defined according to the Sepsis-3 definition), followed by the evaluation of its diagnostic performance via Area Under the Receiver Operating Characteristics (AUROC) analyses. Patients of the sepsis group showed significantly elevated plasma DLL1 levels compared to patients with uncomplicated infections and sterile inflammation. However, patients with infections had significantly higher DLL1 levels than patients with inflammatory diseases. Diagnostic performance was evaluated and showed better performance for DLL1 for the recognition of sepsis (AUC: 0.823; CI 0.731–0.914) than C-reactive protein (AUC 0.758; CI 0.658–0.857), PCT (AUC 0.593; CI 0.474–0.711) and White Blood Cell count (AUC 0.577; CI 0.46–0.694). DLL1 demonstrated promising results for diagnosing sepsis and was able to differentiate sepsis from other infectious and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Ocular involvement in systemic diseases is frequent in cats; however, without concurrent clinical and ophthalmic examinations with gross and/or histologic analysis of the eye, these findings can be underdiagnosed. This article aims to provide gross, histologic, and immunohistochemical characteristics of ocular lesions from cats submitted to necropsy, focusing on those caused by systemic infectious agents. Cats that died due to a systemic infectious disease were selected based on necropsy diagnosis and presence of ocular lesions. Gross, histologic, and immunohistochemical findings were recorded. From April 2018 to September 2019, 849 eyes of 428 cats were evaluated. Histologic abnormalities were seen in 29% of cases, which were classified as inflammatory (41%), neoplastic (32%), degenerative (19%), and metabolic/vascular (8%). Macroscopic changes were present in one-third of eyes with histologic lesions. Of these, 40% were attributed to inflammatory or neoplastic diseases associated with infectious agents. The most important infectious agents causing ocular disease in this study were feline leukemia virus, feline infectious peritonitis virus, and Cryptococcus sp. The most common ocular abnormalities associated with infectious agents were uveitis (anterior, posterior, or panuveitis), optic neuritis, and meningitis of the optic nerve. Ocular lesions secondary to systemic infections in cats are frequent; however, these are not always diagnosed because gross lesions are less common than histologic lesions. Therefore, both gross and histologic evaluation of the eyes of cats is recommended, mainly for cases in which the clinical suspicion or necropsy diagnosis suggests that an infectious agent might be related to the cause of death. [ABSTRACT FROM AUTHOR]

Infections caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) have become a public health emergency. Due to the small therapeutic arsenal available to treat these infections, health agencies have highlighted the importance of developing new antimicrobials against MDR-Ab. In this context, antimicrobial peptides (AMPs) stand out, and animal venoms are a rich source of these compounds. Here, we aimed to summarize the current knowledge on the use of animal venom-derived AMPs in the treatment of MDR-Ab infections in vivo. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eight studies included in this review identified the antibacterial activity of eleven different AMPs against MDR-Ab. Most of the studied AMPs originated from arthropod venoms. In addition, all AMPs are positively charged and rich in lysine residues. In vivo assays showed that the use of these compounds reduces MDR-Ab-induced lethality and bacterial load in invasive (bacteremia and pneumonia) and superficial (wounds) infection models. Moreover, animal venom-derived AMPs have pleiotropic effects, such as pro-healing, anti-inflammatory, and antioxidant activities, that help treat infections. Animal venom-derived AMPs are a potential source of prototype molecules for the development of new therapeutic agents against MDR-Ab. [ABSTRACT FROM AUTHOR]

This review focuses on emerging risk factors for stroke, including air pollution and climate change, gut microbiota, high altitude, and systemic infection. Up to 14% of all stroke-associated mortality is attributed to air pollution and is more pronounced in developing countries. Fine particulate matter and other air pollutants contribute to an increased stroke risk, and this risk appears to increase with higher levels and duration of exposure. Short term air pollution exposure has also been reported to increase the stroke risk. The gut microbiota is a complex ecosystem of bacteria and other microorganisms that reside in the digestive system and affect multiple body systems. Disruptions in the gut microbiota may contribute to stroke development, possibly by promoting inflammation and atherosclerosis. High altitudes have been associated with erythrocytosis and cerebrovascular sinus thrombosis, but several studies have reported an increased risk of thrombosis and ischemic stroke at high altitudes, typically above 3000 m. Systemic infection, particularly infections caused by viruses and bacteria, can also increase the risk of stroke. The risk seems to be greatest in the days to weeks following the infection, and the pathophysiology is complex. All these emerging risk factors are modifiable, and interventions to address them could potentially reduce stroke incidence.

Abstract Background Development of neurodegeneration in older people has been associated with microglial cell activation triggered by systemic infection. We hypothesize that α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulation of this process. Methods 8- to 10-week-old male wild-type (WT) and α7nAChR knock-out (α7nAChR −/−) mice were intraperitoneally inoculated with live Escherichia (E.) coli or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h and killed at 2 or 3 days. The microglial response was characterized by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. To quantify inflammatory response, mRNA expression of pro- and anti-inflammatory mediators was measured in brain and spleen. Results We observed no differences in Iba-1 positive cell number or morphology and flow cytometry (CD11b, CD45 and CD14) of microglial cells between WT and α7nAChR −/− mice after systemic infection. Infected α7nAChR −/− mice showed significantly higher mRNA expression in brain for tumor necrosis factor alpha (TNF-α) at day 2 and 3, interleukin 6 (IL-6) at day 2 and monocyte chemotactic protein 1 (MCP-1) and suppressor of cytokine signaling 1 (SOCS1) at day 3, there was significantly lower mRNA expression in brain for mitogen-activated protein kinase 1 (MAPK1) at day 2 and 3, high-mobility group 1 (HMGB-1) and CD11b at day 2, and deubiquitinase protein A20 (A20) at day 3 compared to infected WT mice. Interpretation Loss of function of α7nAChR during systemic infection led to an increased expression of TNF-α and IL-6 in brain after systemic infection with E. coli, but not to distinct differences in microglial cell number or morphological activation of microglia.

Background and Aim: The coronavirus disease-19 (COVID-19) pandemic caused global economic and health problems. The pandemic increased the number of infectious diseases categorized as neglected diseases, such as staphylococcosis, which is caused by methicillin-resistant Staphylococcus aureus (MRSA). Celery is an herb that consist of antioxidants that can potentially act as antimicrobial agents. This study aimed to analyze the efficacy of celery alcoholic extract against systemic MRSA infections in rat models. Materials and Methods: In this study, 36 male, 6-month-old Sprague-Dawley rats (average weight: 300 g) were used as models. The rats were divided into six groups: Group K– (negative control), Group K+ (infected with MRSA without therapy), Group V (infected with MRSA+100 mg vancomycin per kg body weight [BW]), Group P1 (infected with MRSA+1 mg celery extract per kg BW), Group P2 (infected with MRSA+2 mg celery extract per kg BW), and Group P4 (infected with MRSA+4 mg celery extract per kg BW). The therapy was given once daily for 7 days. Blood and organs were taken on day 7 for hematology, serology, immunohistochemistry, and histopathology. Results: Results showed that 4 mg celery extract per kg BW promotes the healing of MRSA systemic infections in rat models (p≤0.05). The better prognosis was indicated by the normalization of red blood cell indices, white blood cell, neutrophil and lymphocyte counts, Cluster of differentiation 4+, Cluster of differentiation 8+, and Cyclooxygenase-2 expression and absence of severe tissue damage. Celery extracts inhibited MRSA growth in the blood samples. Conclusion: It can be concluded that celery alcoholic extract can potentially be used as an antimicrobial agent against systemic MRSA infections. A clinical study regarding the efficacy of celery extract must be conducted to ensure its potency against MRSA infections in humans.

Plant-infecting viruses utilize various strategies involving multiple viral and host factors to achieve successful systemic infections of their compatible hosts. Lettuce infectious yellows virus (LIYV), genus Crinivirus, family Closteroviridae, has long, filamentous flexuous virions and causes phloem-limited infections in its plant hosts. The LIYV-encoded P26 is a distinct non-virion protein that shows no similarities to proteins in current databases: it induces plasmalemma deposits over plasmadesmata (PD) pit fields and is speculated to have roles in LIYV virion transport within infected plants. In this study, P26 was demonstrated to be a PD-localized protein, and its biological significance was tested in planta by mutagenesis analysis. An LIYV P26 knockout mutant (P26X) showed viral RNA replication and virion formation in inoculated leaves of Nicotiana benthamiana plants, but failed to give systemic infection. Confirmation by using a modified green fluorescent protein (GFP)-tagged LIYV P26X showed GFP accumulation only in infiltrated leaf tissues, while wild-type LIYV GFP readily spread systemically in the phloem. Attempts to rescue P26X by complementation in trans were negative. However a translocated LIYV P26 gene in the LIYV genome rescued systemic infection, but P26 orthologs from other criniviruses did not. Mutagenesis in planta assays showed that deletions in P26, as well as 2 of 11 specific alanine-scanning mutants, abolished the ability to systemically infect N. benthamianaIMPORTANCE Plant viruses encode specific proteins that facilitate their ability to establish multicellular/systemic infections in their host plants. Relatively little is known of the transport mechanisms for plant viruses whose infections are phloem limited, including those of the family Closteroviridae. These viruses have complex, long filamentous virions that spread through the phloem. Lettuce infectious yellows virus (LIYV) encodes a non-virion protein, P26, which forms plasmalemma deposits over plasmodesmata pit fields, and LIYV virions are consistently found attached to those deposits. Here we demonstrate that P26 is a unique movement protein required for LIYV systemic infection in plants. LIYV P26 shows no sequence similarities to other proteins, but other criniviruses encode P26 orthologs. However, these failed to complement movement of LIYV P26 mutants.

Group A Streptococcus (GAS) remains one of the top 10 deadliest human pathogens worldwide despite its sensitivity to penicillin. Although the most common GAS infection is pharyngitis (strep throat), it also causes life-threatening systemic infections. A series of complex networks between host and pathogen drive invasive infections, which have not been comprehensively mapped. Attempting to map these interactions, we examined organ-level protein dynamics using a mouse model of systemic GAS infection. We quantified over 11,000 proteins, defining organ-specific markers for all analyzed tissues. From this analysis, an atlas of dynamically regulated proteins and pathways was constructed. Through statistical methods, we narrowed organ-specific markers of infection to 34 from the defined atlas. We show these markers are trackable in blood of infected mice, and a subset has been observed in plasma samples from GAS-infected clinical patients. This proteomics-based strategy provides insight into host defense responses, establishes potentially useful targets for therapeutic intervention, and presents biomarkers for determining affected organs during bacterial infection.

Background: Advanced neuroimaging demonstrated that neurological involvement occurs in up to 30% of paracoccidioidomycosis (PCM) cases. Current knowledge of neuroparacoccidioidomycosis (NPCM) is based on a 2009 systematic review. However, in the last decade, several new cases have been published, with modern neuroimaging techniques. Objectives: We believe a new systematic review is needed to summarise these advances. Methods: We searched PubMed/MEDLINE, Embase and LILACS for studies from January 2010 to May 2022. Case series and case reports of NPCM were included. We performed a metaproportion to estimate a summary proportion with 95% confidence intervals (CI). Results: Thirty‐four studies including 104 patients were evaluated. We combined our data with the results from the previous review that included 257 cases, totalling 361 patients. We found no new important demographic, clinical or laboratory characteristics. On magnetic resonance imaging (MRI), we found that 72% (95%CI: 38–91) had hyperintensity on T1‐weighted image; 84% (95%CI: 71%–92%) had hypointensity on T2‐weighted image; 80% (95%CI: 66–89) had contrast enhancement with the classical ring‐enhancing pattern. All 8 patients undergoing spectroscopy presented lipid peaks. We found a 16% mortality, lower than in the previous review (44%). Conclusion: NPCM presents a characteristic pattern on MRI that may help to differentiate it from other causes of single or multiple brain lesions. Albeit there is a frequent pattern, it is not specific, as other granulomatous diseases may show similar findings. Advances in neuroimaging with early diagnosis and appropriate management of the disease may have contributed to reducing its mortality. [ABSTRACT FROM AUTHOR]