The hyphal-specific toxin candidalysin promotes fungal gut commensalism

• 成果类型: Article
• 署名作者: Liang, Shen-Huan; Sircaik, Shabnam; Dainis, Joseph; Kakade, Pallavi; Penumutchu, Swathi; Mcdonough, Liam D.; Chen, Ying-Han; Frazer, Corey; Schille, Tim B.; Allert, Stefanie; Elshafee, Osama; Haenel, Maria; Mogavero, Selene; Vaishnava, Shipra; Cadwell, Ken; Belenky, Peter; Perez, J. Christian; Hube, Bernhard; Ene, Iuliana V.; Bennett, Richard J.
• 署名单位: Brown University; University of Pennsylvania; Leibniz Association; Hans Knoll Institute (HKI); Friedrich Schiller University of Jena; University of Texas System; University of Texas Health Science Center Houston; Friedrich Schiller University of Jena; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6308
• DOI: 10.1038/s41586-024-07142-4
• 发表日期: 2024-03-21
• 页码: 620-627
• 关键词: albicans; morphology; colonization; microbiota; morphogenesis; expression; resistance; mycobiota; regulator; DISCOVERY

摘要

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence1-3. Here, we reveal that this paradigm does not apply to multi-kingdom communities in which a complex interplay between fungal morphology and bacteria dictates C. albicans fitness. Thus, whereas yeast-locked cells outcompete wild-type cells when gut bacteria are absent or depleted by antibiotics, hyphae-competent wild-type cells outcompete yeast-locked cells in hosts with replete bacterial populations. This increased fitness of wild-type cells involves the production of hyphal-specific factors including the toxin candidalysin4,5, which promotes the establishment of colonization. At later time points, adaptive immunity is engaged, and intestinal immunoglobulin A preferentially selects against hyphal cells1,6. Hyphal morphotypes are thus under both positive and negative selective pressures in the gut. Our study further shows that candidalysin has a direct inhibitory effect on bacterial species, including limiting their metabolic output. We therefore propose that C. albicans has evolved hyphal-specific factors, including candidalysin, to better compete with bacterial species in the intestinal niche. Both the yeast and hyphal forms of Candida albicans enable colonization of the mammalian gut, with hyphal cells secreting the toxin candidalysin to inihibit bacteria and support fungal commensalism.