Pathogens and disease最新文献

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 inquired 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 why clinically affected dogs are more frequently presented with A. cantonensis haplotype Ac13.

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.

Chlamydia trachomatis and Candida albicans are common inhabitants of the female genital tract. Candida albicans can impact the viability and pathogenesis of some bacteria. Previously, we investigated physical interactions between Ch. trachomatis elementary bodies (EBs) and Ca. albicans. This work indicated that EBs bind to Ca. albicans and become noninfectious by 24 h post-binding. Here, we continue our investigation of these interkingdom, polymicrobial interactions. Candida albicans adheres to bacteria or host surfaces via agglutinin-like sequence or heat shock 70 (Ssa) proteins. Chlamydia trachomatis EBs did not bind Ca. albicans Ssa2 deficient strains as efficiently as wild-type or complemented strains, indicating a role for this protein in chlamydial adherence to Candida. Additionally, Ca. albicans β-glucans inhibit chlamydial infection when exposure occurs during EB adsorption onto cervical cells. Laminarin, a β-glucan agonist of the C-type lectin receptor Dectin-1, inhibited chlamydial infection in both cervical epithelial cells and mice when exposure occurred prior to, during, or immediately following EB inoculation. Conversely, a Dectin-1 antagonist laminarin did not inhibit infection in vitro, suggesting that β-glucan inhibition of Ch. trachomatis requires C-type lectin receptor signaling. Overall, our data demonstrate that β-glucans from multiple species, including Ca. albicans, inhibit Chlamydia via stimulation of host-signaling pathways.

Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.

Chlamydia trachomatis infection can be regulated by autophagy-related genes. LncRNA CYTOR has been proven to be involved in autophagy. In this research, we investigated the role of CYTOR in autophagy induced by C. trachomatis and the potential mechanisms. After C. trachomatis infection, CYTOR and MAPK1 were up-regulated and miR-206 was down-regulated, meanwhile, the autophagy-related protein Beclin1 and LC3-Ⅱ/LC3-Ⅰ ratio were increased. Interference with CYTOR or overexpression with miR-206 downregulated the autophagy-related protein Beclin1 and the number of autophagic spots LC3, decreased the protein ratio of LC3-II/LC3-I, and upregulated the expression of P62 protein. The luciferase reporter assay confirmed that CYTOR acted as a sponge for miR-206 to target MAPK1. In addition, CYTOR promoted autophagy induced by C. trachomatis infection through the MAPK1/ERK signaling pathway activation. Taken together, we have identified a novel molecular mechanism that the CYTOR/miR-206/MAPK1 axis was involved in the regulation of autophagy in C. trachomatis infection. This work provides an experimental basis for elucidating the pathogenesis of C. trachomatis for the treatment, prevention and control of related infectious diseases.

Post-streptococcal glomerulonephritis (PSGN) is primarily associated with preceding group A streptococcal skin or throat infections, now mainly observed in economically disadvantaged communities. This condition significantly predisposes individuals to later-life chronic kidney disease and concurrent renal complications, with the elderly experiencing increased severity and less favourable outcomes. Streptococcal pyrogenic exotoxin B and nephritis-associated plasmin receptor are identified nephritogenic antigens (nephritogens). Pathogenesis of PSGN is multifactorial. It can involve the formation of antigen-antibody immune complexes, causing inflammatory damage to renal glomeruli. Deposition of circulating immune complexes or in situ formation of immune complexes in glomeruli, or both, results in glomerulonephritis. Additionally, molecular mimicry is hypothesized as a mechanism, wherein cross-reactivity between anti-streptococcal antibodies and glomerular intrinsic matrix proteins leads to glomerulonephritis. Besides, as observed in clinical studies, streptococcal inhibitor of complement, a streptococcal-secreted protein, can also be associated with PSGN. However, the interplay between these streptococcal antigens in the pathogenesis of PSGN necessitates further investigation. Despite the clinical significance of PSGN, the lack of credible animal models poses challenges in understanding the association between streptococcal antigens and the disease process. This review outlines the postulated mechanisms implicated in the development of PSGN with possible therapeutic approaches.

Tuberculosis (TB) continues to pose a significant global health challenge, emphasizing the critical need for effective preventive measures. Although many studies have tried to develop new attenuated vaccines, there is no effective TB vaccine. In this study, we report a novel attenuated Mycobacterium tuberculosis (M. tb) strain, CHVAC-25, cultured continuously for 25 years in the laboratory. CHVAC-25 exhibited significantly reduced virulence compared to both the virulent H37Rv strain in C57BL/6J and severe combined immunodeficiency disease mice. The comparative genomic analysis identified 93 potential absent genomic segments and 65 single nucleotide polymorphic sites across 47 coding genes. Notably, the deletion mutation of ppsC (Rv2933) involved in phthiocerol dimycocerosate synthesis likely contributes to CHVAC-25 virulence attenuation. Furthermore, the comparative analysis of immune responses between H37Rv- and CHVAC-25-infected macrophages showed that CHVAC-25 triggered a robust upregulation of 173 genes, particularly cytokines crucial for combating M. tb infection. Additionally, the survival of CHVAC-25 was significantly reduced compared to H37Rv in macrophages. These findings reiterate the possibility of obtaining attenuated M. tb strains through prolonged laboratory cultivation, echoing the initial conception of H37Ra nearly a century ago. Additionally, the similarity of CHVAC-25 to genotypes associated with attenuated M. tb vaccine positions it as a promising candidate for TB vaccine development.

Cutaneous burn trauma, compromise of dermal layers and immune defense system is a physical and fiscal burden on healthcare systems. Burn-wound infections are a serious complication of thermal injury and contribute significantly to care burden. After burn-induced trauma, sepsis by Pseudomonas aeruginosa impairs patient recovery and contributes to mortality and morbidity. Past studies show positive correlation between detection of Pseudomonas species and healing-impaired traumatic wounds. Pseudomonas aeruginosa is a resilient opportunistic human pathogen and a nosocomial agent involved in pathology of healing-impaired wounds, especially in burn patients. Expansive array of virulence determinants has resulted in gentamicin- and silver-resistant P. aeruginosa outbreaks. Knowledge of molecular dynamics and phylogeny of P. aeruginosa associated with burn wounds is limited. Therefore, we conducted whole-genome sequencing for genotyping and phylogenetic analysis of P. aeruginosa burn-associated strains (n = 19) isolated from 7 burn cases during hospitalization. Comparison of genetic features in P. aeruginosa strains in the core genome and mobilome detected genetic variations within some clonal infections over time. Genetic variations were observed among different burn cases, with some features identified in severe lung infections. Polyclonal infections were also observed, with differing genotypes and virulence potentials, highlighting the importance of reasoned sampling of isolates for clinical testing.