Pathogens and disease最新文献

BK polyomavirus (BKPyV) infection reactivates with immunosuppressive therapies and can lead to the development of BKPyV-associated nephropathy (BKPyVAN) in kidney transplant recipients. This scoping review assesses the use of transcriptomics to profile BKPyVAN in kidney transplant recipients. The following search strategy was employed in Medline and Embase: 'BK virus' or 'BK polyomavirus' or 'Polyomavirus' AND 'Kidney transplant' or 'Nephritis' or 'Nephropathy' AND 'Gene expression' or 'Transcriptomics' or 'mRNA'. The search identified 368 publications (264 EMBASE and 104 MEDLINE), and after removal of duplicates (92) and abstract/full-text screening, there were 11 eligible studies which included 7 original transcriptomic studies and 4 bioinformatic studies. There was consistent dysregulated expression of proinflammatory pathways (e.g. cytokines, chemokines, T- and B-cell-related pathways) in BKPyVAN compared with stable graft function. There was considerable overlap between the gene expression patterns identified in BKPyVAN and T-cell mediated rejection that require more exploration. This review highlights limitations including small sample sizes, lack of validation, and variation in technical platforms and study designs. Transcriptomics in BKPyVAN is currently underutilized and there is a genuine need for further research in larger cohorts to provide action in discovering novel therapeutic targets and discriminative gene expression signatures to guide individualized therapeutic strategies.

The obligate intracellular Gram-negative bacterium Chlamydia psittaci, a zoonotic pathogen transmissible between birds and humans, has played a pioneering role in research on its membrane-bound replicative niche termed the inclusion. Inclusion membrane proteins (Inc proteins) are crucial for Chlamydia-host interactions and were first identified in C. psittaci. This study investigates putative C. psittaci Inc proteins by a combination of in silico analyses, immunofluorescence and, strikingly, a new Inc/GFP chimera protein-based interactomics approach to identify host cellular interaction partners. Here, we report a novel C. psittaci Inc protein, Cps0558, along with respective host cellular interaction partners, in particular ACAD11, which is involved in lipid metabolism. We confirm their physical interaction in the native infection context, supporting the physiological relevance of our chimera-based screen. Furthermore, new interaction partners for the known Inc protein IncA are identified, revealing a potential role of IncA as modulator of the host ubiquitylation system. These results provide further insights into the biology of C. psittaci and present a novel tool for studying Inc proteins under conditions closely resembling their natural tertiary structure.

Inflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecal Candida yeasts. Ongoing research indicates that genetic and phenotypic diversity of Candida albicans may be linked with disease severity. Here, we set out to investigate feces-derived C. albicans strains from individuals with IBD and healthy volunteers through microsatellite-based genotyping and phenotypic assays. A seven-locus microsatellite panel was applied, of which six loci were newly developed. It appears that there is no specific lineage of C. albicans that is associated with IBD, but rather that the three study populations (Crohn's disease, ulcerative colitis, healthy volunteers) do have distinguishable distributions of genotypes. In addition, phenotypic characterization by means of enzyme release assays revealed trends between genotypes, virulence-related enzyme activity, and clinical biomarkers. We thus show that microsatellite typing can describe genetic diversity of feces-derived C. albicans strains, and that phenotypic diversity of these strains may indeed correlate with fungal genotype or disease. This study opens further possibilities to investigate fecal fungi in relation to severity of inflammation in IBD or in other (intestinal) diseases.

The rat lungworm (Angiostrongylus cantonensis) is an invasive parasite of rats that in accidental hosts, such as dogs and humans, causes eosinophilic meningitis. In Australia, only two distinct rat lungworm cox1 haplotypes have been detected in clinically affected dogs, with haplotype Ac13 implicated in most cases. Using locally sourced isolates, we enquired whether the brain migrating larvae elicit different host response in its natural host. We examined brain transcriptome, faecal shedding rates, and adult worm of A. cantonensis isolates representing two distinct cox1 haplotypes, SYD.1 and Ac13 (represented by isolate SYD.2), in experimentally infected Wistar rats. For SYD.1-infected rats, only one differentially expressed gene (DEG) was upregulated in the compared to controls. In contrast, the transcriptome of SYD.2-infected rats included 100 DEGs, with enrichment of functional terms related to immune response, neuroactivity, and signalling. Faecal shedding did not differ between SYD.1- and SYD.2-infected rats, but adult worm burdens were higher in the SYD.1 group. The increased immune response in SYD.2-infected rats provides evidence that there is strain specific virulence that is pronounced in its natural host. This study provides initial parasite-specific evidence explaining why clinically affected dogs are more frequently presented with A. cantonensis haplotype Ac13.

The respiratory epithelium serves as initial defense against airborne pathogens through its barrier function and induction of immune responses. To study epithelial-pathogen interactions, we used primary epithelial models that closely resembled the epithelia of the airways, for which we collected nasal (n = 7), nasopharyngeal (n = 3), and bronchial (n = 4) epithelial cells from different donors. We cultured these epithelial cells on an air-liquid interface and evaluated their differentiation status. To assess how the different epithelial models respond to distinct types of exposures, the cells were stimulated with IFN-γ, Streptococcus pneumoniae, Neisseria meningitidis, or respiratory syncytial virus (RSV) for 72 h. The nasopharyngeal epithelium was distinct from nasal and bronchial cells with respect to morphology, pathogen load, and induction of cytokine responses, while nasal and bronchial epithelial cells had similar, but not identical cytokine profiles. Each tissue type and stimulus showed specific cytokine patterns. Interestingly, donor-specific differences for IFN-λ2,3 and IL-6 responses were found during meningococcal and RSV infections. Our data highlight morphological differences and a broad variety of epithelial cytokine responses in the different regions of the upper respiratory tract. These different epithelial models will help unravel why some pathogens target specific respiratory regions and why certain individuals are more susceptible to infections.

Vibrio cholerae remains a significant public health threat in Sub-Saharan Africa and the East Mediterranean Region, where recurrent outbreaks are driven by inadequate water, sanitation, and hygiene infrastructure, climatic variability, and socio-political instability. This review explores the persistence of the pathogen in these regions, examining its epidemiology, environmental reservoirs, and genomic adaptations that enhance its survival and transmission. We highlight the impact of antimicrobial resistance and the role of climate change in cholera dynamics. Furthermore, we discuss current prevention and control strategies, including advancements in oral cholera vaccines, genomic surveillance, and microbiome-targeted interventions. Addressing these challenges requires a multifaceted approach that integrates sustainable sanitation improvements, strengthened disease surveillance, and innovative vaccination strategies. Understanding the persistence of V. cholerae in these high-risk regions is critical for developing effective, long-term mitigation strategies to reduce cholera morbidity and mortality.

Sepsis is a life-threatening condition characterized by immunosuppression, largely mediated by endotoxin tolerance. Akkermansia muciniphila (AKK), a gut probiotic, has been shown to modulate immune responses. In this study, 16S rRNA sequencing revealed decreased AKK levels in immunosuppressed individuals. In vitro experiments using RAW 264.7 macrophages demonstrated that endotoxin tolerance induced an M2 phenotype, which was reversed by AKK treatment, promoting an M1 phenotype. Additionally, AKK enhanced bacterial clearance of Pseudomonas aeruginosa. In vivo, AKK administration alleviated immunosuppression in an endotoxin-tolerant mouse model by modulating macrophage phenotypes. These findings highlight AKK as a potential therapeutic candidate for sepsis-induced immunosuppression.

We reported earlier about development of nano-formulation of an essential oil "eugenol" through its entrapment within animal protein "gelatin," using a simple ultrasonication technique, followed by purification via ultracentrifugation. The synthesized eugenol nanoparticle (ENP) exhibited promising antibacterial and antibiofilm activity on pathogenic strain Pseudomonas aeruginosa MTCC 2488 in vitro. Here, we report on in vivo therapeutic efficacy of ENP against Pseudomonas-administered lung infection, developed in BALB/c mice. Our findings revealed that ENP treatment significantly reduced bacterial burden in infected lung tissues and promoted recovery from infection-associated weight loss, hypothermia, and fluid accumulation in mice. In addition, histopathological and immunological studies showed that the elevated level of inflammatory cytokines TNF-α, IL-1β, MCP-1, GM-CSF, and IFN-γ in lung tissue, serum, and broncho-alveolar lavage (BAL) fluid of Pseudomonas-infected mice were considerably attenuated to almost normal level by ENP treatment. Notably, free eugenol had not so high antipseudomonal action as ENP.