Hyphae promote Candida albicans fitness and commensalism in the gut - Nature.com
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Fungi are commensal members of the human microbiota, for instance in the intestinal niche. However, they can also assume pathological roles and can cause life-threatening systemic infections. Candida albicans colonizes the human gastrointestinal tract, and previous data suggested that the yeast morphological form of the fungus promotes colonization and commensalism, whereas a yeast-to-hyphal transition and filamentation is detrimental to commensal fitness in standard colonization models, but important for tissue invasion and infection. Given the negative effect of filamentation on fungal fitness in the gut, it is unclear why filamentation has been retained. In this study, Bennett, Hube and colleagues now show that hyphae formation is critical for C. albicans gut colonization in the presence of commensal bacteria owing to the production of a hyphal-associated factor.
The authors went on to investigate the possible factors involved in the fitness advantage of filamentation-competent cells over yeast-locked C. albicans cells in the gut. They report that deletion of the hyphal-specific gene ECE1, which encodes the peptide toxin candidalysin, resulted in a fitness defect compared with the wild type in antibiotic-naive hosts but not in antibiotic-treated or germ-free mice. Moreover, the fitness advantage of wild-type cells over ECE1-deletion mutant cells was restored in germ-free mice that had been pre-colonized with Escherichia coli, further suggesting that bacterial levels have a role in the fitness advantage. To determine the possible mechanisms whereby candidalysin affects gut commensalism, the authors tested the direct effect of a synthetic candidalysin peptide on bacterial species. Interestingly, candidalysin peptide significantly inhibited the growth of E. coli, Klebsiella pneumoniae and Enterococcus faecium. Moreover, candidalysin decreased the metabolic activity of these bacterial species. Therefore, candidalysin not only causes host cell damage and inflammation, as previously established, but the fungal factor also directly inhibits the growth and metabolism of commensal bacterial species that are competing for resources with C. albicans.
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References
Original article
Liang, S.-H. et al. The hyphal-specific toxin candidalysin promotes fungal gut commensalism. Nature https://doi.org/10.1038/s41586-024-07142-4 (2024)
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