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

The fungal pathogen Candida albicans colonizes the human gut, where short-chain fatty acids (SCFAs) serve as a source of carbon. This fungus harbors one of the largest microbial families of ATO (acetate transporter 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 colonization 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 colonization, in part through SCFA utilization.IMPORTANCEThe human gut is rich in microbial fermentation products such as short-chain fatty acids (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 (acetate transporter ortholog) 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 colonization 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.