Biology subjects

Ost, K. S.

Publications and source records attributed to Ost, K. S..

4 recordsLinked to original sources

bioRxiv2026

A Candida glabrata adhesin-like effector drives fitness and immunogenicity in the gut

Candida glabrata is a leading cause of invasive candidiasis. The gut serves as its primary reservoir, yet factors governing colonization and pathogenic potential remain poorly defined. Here, we identify immunoglobulin A (IgA) as a key regulator of C. glabrata within the intestinal microbiome. We found that C. glabrata induces an IgA response in a strain-specific manner. Comparative transcriptional and proteomic analyses of IgA-inducing and non-inducing strains identified a putative adhesin, Awp11, whose expression correlated with IgA induction. Awp11 is directly targeted by IgA and is required for inducing C. glabrata-specific IgA and Th17 responses in vivo. Functionally, Awp11 promotes colonization of a complex intestinal microbiome, and intestinal IgA limits this advantage. In most strains, AWP11 transcription is dynamic and limited by IgA in the gut. This identifies Awp11 as a key determinant of strain-dependent immunogenicity and gut colonization that C. glabrata may dynamically regulate to balance colonization and immune evasion.

immunology↗

bioRxiv2025

A fungal pathobiont promotes Streptococcus agalactiae vaginal persistence and pathogenesis through physical and metabolic interactions

Complex polymicrobial interactions at the host interface can shape the mucosal landscape and tip the scales between commensalism and pathogenicity. Here, we use a newly adapted murine model of vaginal colonization to show that the human pathobiont Candida albicans (Ca) supports Group B Streptococcus (GBS) fitness in the vaginal tract and ascension to the uterus. GBS frequently colonizes the vagina asymptomatically; however, during pregnancy, colonization can lead to adverse outcomes and neonatal invasive infection. Using human vaginal isolates of Ca and GBS, we demonstrate that physical interactions contribute to persistence. Triple RNA sequencing of Ca, GBS, and a physiologically relevant model of the human vaginal epithelium reveals that GBS induces arginine biosynthesis in Ca. This drives the expression of bacterial virulence factors and primes GBS for adhesion to the epithelium. We show that interkingdom nutrient exchange can increase GBS pathogenic potential and identify a new target for preventative therapies.

microbiology↗

bioRxiv2025

Bacterial metabolites induce cell wall remodeling, antifungal resistance, and immune recognition of commensal fungi

The fungus Candida albicans commensally colonizes mucosal surfaces in healthy individuals but can cause both superficial mucosal and life-threatening disseminated infections. The balance between commensalism and pathogenicity is complex and depends on factors including host and fungal genetic background, the host environment, and fungal interactions with local microbes. The major interaction interface of C. albicans with the host is its multilayered cell wall, which is dynamic and highly responsive to the surrounding environment. Therefore, factors that influence the fungal cell wall will directly impact C. albicans-host interactions. Our work demonstrates that multiple physiologically-relevant gastrointestinal bacteria influence fungal cell wall composition during co-culture with C. albicans, including as complex communities derived from the gut. Using Escherichia coli as a model, we show that bacterial-induced fungal cell wall remodeling occurs rapidly and is mediated by secreted bacterial metabolite(s). Fungal mutant analysis revealed that the high osmolarity glycerol (HOG) pathway, which is critical for responding to environmental stresses, has an important role in regulating this cell wall remodeling phenotype through the Sln1 histidine kinase. Importantly, bacterial-mediated fungal cell wall remodeling increases C. albicans resistance to the echinocandins, increases recognition by both dectin-1 and dectin-2, and decreases recognition by human IgA. Overall, this work comprehensively characterizes an interaction between C. albicans and common gastrointestinal bacteria that has important implications for fungal biology and host interactions.

microbiology↗

bioRxiv2024

Stress-driven emergence of heritable non-genetic drug resistance

Drug resistance is the chief cause of treatment failure for therapies targeting chronic and infectious diseases. Whether the emergence of resistance is accelerated by environmental exposure to low levels of therapeutics remains controversial. Here, we report a non-genetic mechanism of stress adaptation that promotes heritable resistance to the widely used antifungal drug fluconazole. In the human fungal pathogen Candida albicans, transient exposure to subtherapeutic fluconazole doses induces a protective response that we term para-resistance. Like conventional resistance mechanisms, para-resistance is heritable. However, it does not arise from genetic mutations and can revert spontaneously. Systematic analyses of para-resistant isolates suggest that its key regulators include the stress-activated MAP kinase Hog1, the histone deacetylase subunit Snt1, the chromatin regulator Rap1, and the Sko1 transcriptional factor. Notably, molecules that disrupt biomolecular condensation and prion propagation - crucial for the inheritance of protein assemblies - block the induction of para-resistance, whereas inhibiting histone deacetylases facilitates its induction. We find that para-resistance is common in clinical isolates and, remarkably, passage through the mammalian gut triggers its acquisition, compromising fluconazoles therapeutic efficacy. Our work defines a pervasive, prion-like epigenetic mechanism of stress adaptation and highlights potential strategies to mitigate the rapid emergence of drug resistance.

microbiology↗