Biology subjects

Wijnants, S.

Publications and source records attributed to Wijnants, S..

4 recordsLinked to original sources

bioRxiv2025

Vitamin B2 Production by Vaginal Lactobacilli Promotes Symbiosis

The human vaginal microbiome, particularly with lactobacilli as the main inhabitants, plays a key role in maintaining womens health. While lactic acid-mediated pathogen exclusion is well known, broader metabolic functions of vaginal lactobacilli remain underexplored. In this study, we analyzed the vaginal microbiome and metabolome of 258 healthy women from the Isala program. Using targeted metabolomics analysis, we detected a high prevalence with strong interpersonal differences of most B-vitamins, their precursors, and vitamin A in the vaginal microenvironment. Riboflavin (B2) and biotin (B7) showed strong associations with Lactobacillus crispatus and Limosilactobacillus sp. Comparative genomics, phenotypic assays, and in vivo metatranscriptomic data (VIRGO2) collectively confirmed riboflavin biosynthesis by these taxa. Using a riboflavin overproducing Lim. reuteri as a functional model, we showed that microbially derived riboflavin and its pathway intermediates are transported across the vaginal epithelium and modulate host redox balance, cytokine production, and activation of mucosal-associated invariant T (MAIT) cells via induction of MR1 (Major histocompatibility complex, class I-related protein receptor), revealing a potential immunometabolic interface between the vaginal microbiota and its host.

microbiology↗

bioRxiv2025

The ATO gene family governs Candida albicans colonisation in the dysbiotic gastrointestinal tract

The fungal pathogen Candida albicans colonises the human gut where short-chain fatty acids (SCFAs) offer sources of carbon. This fungus harbours one of the largest microbial families of ATO (Acetate Transport Ortholog) genes, which encode putative SCFA transport proteins. Here, we generate C. albicans null mutants lacking individual or all known putative SCFA transporter genes and compare their phenotypes in vitro and in vivo. We show that blocking ATO function in C. albicans impairs SCFA uptake and growth, particularly on acetate. The uptake of acetate is largely dependent on a functional Ato1 (also known as Frp3/Ato3) and it is effectively abolished upon deletion of all ATO genes. We further demonstrate that deletion of the entire ATO gene family, but not inactivation of ATO1 alone, compromises the stable colonisation of C. albicans in the murine gastrointestinal tract following bacterial disruption by broad-spectrum antibiotics. Our data suggest that the ATO gene family has expanded and diversified during the evolution of C. albicans to promote the fitness of this fungal commensal during gut colonisation, in part through SCFA utilisation. IMPORTANCEThe human gut is rich in microbial fermentation products such as SCFAs, which serve as key nutrients for both bacteria and fungi. C. albicans, a common fungal resident of the gut and a cause of opportunistic infections, carries an unusually large family of ATO genes. This study reveals that this ATO gene family is required for the efficient uptake of acetate, the most abundant SCFA in the gut, and for stable colonisation of the gut. These findings uncover a new layer of metabolic adaptation in fungal commensals of humans and suggest that transporter gene expansion can shape microbial fitness in response to environmental nutrient signals.

microbiology↗

bioRxiv2024

The stress-protectant molecule trehalose mediates fluconazole tolerance in Candida glabrata

The incidence of non-albicans Candida infections has witnessed a substantial rise in recent decades. Candida glabrata (Nakaseomyces glabratus), an opportunistic human fungal pathogen, is accountable for both superficial mucosal and life-threatening bloodstream infections, particularly in immunocompromised individuals. Distinguished by its remarkable resilience to environmental stressors, C. glabrata exhibits intrinsic tolerance to azoles and a high propensity to swiftly develop azole resistance during treatment. The molecular mechanism for the high tolerance is not fully understood. In this work we investigated the possible role of trehalose in this tolerance. We generated mutants in the C. glabrata TPS1, TPS2, and NTH1 genes, encoding trehalose 6-phosphate synthase (Tps1), trehalose 6-phosphate phosphatase (Tps2), and neutral trehalase (Nth1), respectively. As expected, the tps1{Delta} strain cannot grow on glucose. The tps2{Delta} strain demonstrated diminished trehalose accumulation and very high levels of trehalose 6-phosphate (T6P), the biosynthetic intermediate, in comparison to the WT strain. Whereas these higher T6P levels did not affect growth, the lower trehalose levels clearly resulted in lower environmental stress tolerance and a lower susceptibility to fluconazole. More interestingly, the tps2{Delta} strain completely lost tolerance to fluconazole, characterized by the absence of slow growth at supra-MIC concentrations of this drug. All these phenotypes are reversed in the nth1{Delta} strain, which accumulates high levels of trehalose. Our findings underscore the role of trehalose in enabling tolerance towards fluconazole in C. glabrata. We further show that the change in tolerance is a result of the effect that trehalose has on the sterol pattern in the cell, showing that accumulation of toxic sterols correlate with absence of tolerance. Author summaryC. glabrata is a yeast of significant medical importance, known for causing nosocomial outbreaks of invasive candidiasis. Its propensity to develop resistance to antifungal medications, notably azoles such as fluconazole, raises considerable concern. An underlying reason for the rapid development of resistance is its intrinsic tolerance to this drug. The underlying molecular mechanism of tolerance to fluconazole is heavily studied but not understood. This study sheds light on the involvement of trehalose in modulating tolerance to fluconazole. We have elucidated that trehalose serves not only as a protective agent against various stresses but also as a mediator of fluconazole resistance and tolerance. To start elucidating how this may work, we provide data that trehalose (or the enzymes affecting the amount of trehalose in the cell) alters the ergosterol type and level in the cells, thereby affecting tolerance.

microbiology↗

bioRxiv2022

Differential sensing by the C. albicans Gpr1 receptor results in morphogenesis, β-glucan masking and survival in macrophages

The human fungal pathogen, Candida albicans, is very proficient at several classical virulence factors such as morphogenesis, adhesion, biofilm formation and immune evasion through {beta}-glucan masking. The protein kinase A (PKA) pathway is involved in both morphogenesis and {beta}-glucan masking. Several signals converge onto the PKA pathway, but it contains only a single upstream G-protein coupled receptor, Gpr1. We identified specific residues within the N-terminal tail of Gpr1 that are required for methionine-induced morphogenesis through Tpk2. Furthermore, we observe that Gpr1-Gpa2 has an active role in exposing glucans. Even though Gpr1 is required for survival when C. albicans is challenged with macrophages, specifically disrupting morphogenesis did not attenuate this survival. Additionally, constitutive {beta}-glucan masking did not improve C. albicans survival rates in the macrophage assay. Taken together, this indicates that Gpr1 may regulate additional mechanisms, possibly through glutamine 461, which are crucial in a macrophage context. Significance StatementCandida albicans is a human fungal pathogen mostly present as a commensal in the gastrointestinal tract. It can rapidly adapt to its everchanging environment through continuous monitoring of extracellular signals. These extracellular signals include methionine and lactate which induce respectively morphogenesis and {beta}-glucan masking through the G-protein coupled receptor, Gpr1. Through a mutagenic approach we different amino acids of the receptor sense methionine and/or lactate but we show that Gpr1 may have an additional ligand that affect its survival in macrophages.

microbiology↗