TheATOgene family governsCandida albicanscolonisation in the dysbiotic gastrointestinal tract
Abstract
The fungal pathogenCandida albicanscolonises the human gut where short-chain fatty acids (SCFAs) offer sources of carbon. This fungus harbours one of the largest microbial families ofATO(Acetate Transport Ortholog) genes, which encode putative SCFA transport proteins. Here, we generateC. albicansnull mutants lacking individual or all known putative SCFA transporter genes and compare their phenotypesin vitroandin vivo. We show that blockingATOfunction inC. albicansimpairs 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 allATOgenes. We further demonstrate that deletion of the entireATOgene family, but not inactivation ofATO1alone, compromises the stable colonisation ofC. albicansin the murine gastrointestinal tract following bacterial disruption by broad-spectrum antibiotics. Our data suggest that theATOgene family has expanded and diversified during the evolution ofC. albicansto promote the fitness of this fungal commensal during gut colonisation, in part through SCFA utilisation.
IMPORTANCE
The 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 ofATOgenes. This study reveals that thisATOgene 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.
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