Normal Adaptation of Candida albicans to the Murine Gastrointestinal Tract Requires Efg1p-Dependent Regulation of Metabolic and Host Defense Genes

Abstract

ABSTRACTAlthough gastrointestinal colonization by the opportunistic fungal pathogenCandida albicansis generally benign, severe systemic infections are thought to arise due to escape of commensalC. albicansfrom the gastrointestinal (GI) tract. TheC. albicanstranscription factor Efg1p is a major regulator of GI colonization, hyphal morphogenesis, and virulence. The goals of this study were to identify the Efg1p regulon during GI tract colonization and to compareC. albicansgene expression during colonization of different organs of the GI tract. Our results identified significant differences in gene expression between cells colonizing the cecum and ileum. During colonization,efg1−null mutant cells expressed higher levels of genes involved in lipid catabolism, carnitine biosynthesis, and carnitine utilization than did colonizing wild-type (WT) cells. In addition, during laboratory growth,efg1−null mutant cells grew to a higher density than WT cells. Theefg1−null mutant grew in depleted medium, while WT cells could grow only if the depleted medium was supplemented with carnitine, a compound that promotes the metabolism of fatty acids. Altered gene expression and altered growth capability support the ability ofefg1−cells to hypercolonize naïve mice. Also, Efg1p was shown to be important for transcriptional responses to the stresses present in the cecum environment. For example, during colonization,SOD5, encoding a superoxide dismutase, was highly upregulated in an Efg1p-dependent manner. Ectopic expression ofSOD5in anefg1−null mutant increased the fitness of theefg1−null mutant cells during colonization. These data show thatEFG1is an important regulator of GI colonization.