The Transcriptional Response of to Weak Organic Acids, Carbon Source, and Inactivation Unveils a Role for in Mediating the Fungistatic Effect of Acetic Acid

is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal (GI) microbiota were shown to keep colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displays a synergistic effect with the absence of glucose in medium of culture, which underlines the complex interactions that faces in its natural environment. Inactivation of the transcriptional regulator in results in a lack of sensitivity to this synergistic outcome. To decipher transcriptional responses to glucose, WOAs, and the role of , we performed RNA sequencing (RNA-seq) on four biological replicates exposed to combinations of these three parameters. We were able to characterize the (i) glucose response, (ii) response to acetic and butyric acid, (iii) regulation of , and (iv) genes responsible for WOA resistance. We identified a group of six genes linked to WOA sensitivity in a glucose--dependent manner and inactivated one of these genes, the putative glucose transporter , in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOA resistance in the absence of glucose. This result points toward a mechanism of WOA sensitivity in involving membrane transporters, which could be exploited to control yeast colonization in human body niches.