Pathogens and disease最新文献

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.

Pneumocystis jirovecii pneumonia (PJP) has significant mortality, especially in immunocompromised hosts without underlying human immunodeficiency virus infection (HIV). Inflammatory phenotypes may influence clinical outcomes. This study examines the relationship between inflammation, as measured by C-reactive protein (CRP), and adverse outcomes in HIV-negative patients with PJP. A retrospective analysis was conducted on 62 HIV-negative patients with presumed or confirmed PJP from 2006 to 2023. CRP measured within 48 hours of admission were used to classify patients into hypo-inflammatory (CRP<30 mg/l), normo-inflammatory (30-135 mg/l), and hyper-inflammatory (>135 mg/l) groups. Composite adverse outcomes (defined as all-cause in-hospital mortality or mechanical ventilation) were compared across groups using univariate and multivariable analyses. The inflammatory groups differed in CRP but not significantly in terms of white cell count, ferritin, or lactate dehydrogenase. Corticosteroid use was similar across groups. Adverse outcomes occurred in 37.5% of the hypo-inflammatory group, 20.0% of the normo-inflammatory group, and 68.8% of the hyper-inflammatory group (P = 0.005). Hyper-inflammation independently predicted adverse outcomes (adjusted OR 6.98, 95% CI 1.81-26.92, P = 0.005). This study raises the possibility of a U-shaped relationship between inflammatory phenotypes and outcomes in PJP, with hypo- and hyper-inflammatory phenotypes associated with worse outcomes.

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.

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.

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.