Microorganisms

Endocytic trafficking in Candida albicans is a fundamental cellular process that is crucial for its secretion, filamentation, and virulence-related processes. We have previously demonstrated that loss of the key endocytosis-related C. albicans gene END3 disrupts clathrin-mediated endocytosis, leading to impairments in actin patch formation, filamentation, biofilm formation, cell wall integrity, and extracellular protease secretion. The end3 null mutant also exhibits altered antifungal susceptibility and reduced host-cell damage in an in vitro keratinocyte infection model. To ascertain whether endocytosis is required for virulence in vivo, we assessed virulence of the C. albicans end3 null mutant in a murine model of disseminated candidiasis. After infection via the tail vein, and analysis of host survival over 28 days, the end3 null mutant was markedly hypovirulent compared to corresponding control strains. These results indicate that endocytosis mediated by END3 in C. albicans contributes to pathogenesis in vivo.

Invasive fungal diseases (IFDs) represent an escalating global health threat, compounded by the rapid emergence of antifungal resistance (AFR). This review synthesizes the contemporary landscape of AFR from clinical and microbiological perspectives, providing actionable insights for clinical practitioners. We examine the epidemiology of critical pathogens, including Candidozyma auris, clonal Candida parapsilosis, azole-resistant Aspergillus fumigatus, and dissect the underlying molecular mechanisms, from genetic mutations in ERG11 and cyp51A to novel emerging epigenetic and adaptive strategies. We critically appraise the diagnostic gap between phenotypic testing and clinical urgency, highlighting the role of rapid molecular assays and next-generation sequencing. Finally, we evaluate evidence-based therapeutic strategies, including the integration of novel agents such as rezafungin, ibrexafungerp, olorofim, and fosmanogepix), while emphasizing the imperative of antifungal stewardship, infection prevention and control in mitigating resistance, and “One-Health” interventions.

The DNA methylation landscape in the lungs of argali hybrid sheep infected with Mycoplasma ovipneumoniae (Mo) remains poorly characterized. This study aimed to profile genome-wide DNA methylation using reduced representation bisulfite sequencing (RRBS) and to validate key genes using bisulfite sequencing PCR (BSP), methylation-specific PCR (MSP), and quantitative MSP (QMSP). The results revealed a significant increase in global mCG methylation in -infected lungs. RRBS identified 3691 differentially methylated regions (DMRs), 66.2% of which were hypermethylated. Methylation levels were highest in gene bodies/downstream regions and lowest in promoters/5′ untranslated regions. Differentially methylated genes (DMGs) were enriched in immune–inflammatory pathways (e.g., antigen presentation, B-cell receptor signaling, Th17 differentiation) and, to a lesser extent, neural signaling pathways. BSP confirmed the methylation status of hypermethylated (KHDC3L, GILT, OVAR-DRB1, SGK1, ADAM17) and hypomethylated (EFCAB11, AP1B1, TATDN1) DMGs. Independent validation by MSP and QMSP further supported the hypermethylation of SGK1 and GILT in both lung tissue and alveolar macrophages. Quantitative reverse-transcription PCR showed that promoter hypermethylation of KHDC3L, GILT, SGK1, and ADAM17 was associated with transcriptional downregulation, while hypomethylation of AP1B1 correlated with upregulation. In summary, Mo infection induces genome-wide hypermethylation reprogramming that dysregulates key immune-related genes, highlighting potential epigenetic mechanisms in the pathogenesis of mycoplasmal pneumonia.