Aneuploidy and gene dosage regulate filamentation and host colonization by <i>Candida albicans</i>.

Abstract

Aneuploidy is a frequent occurrence in fungal species where it can alter gene expression and promote adaptation to a variety of environmental cues. Multiple forms of aneuploidy have been observed in the opportunistic fungal pathogen <i>Candida albicans,</i> which is a common component of the human gut mycobiome but can escape this niche and cause life-threatening systemic disease. Using a barcode sequencing (Bar-seq) approach, we evaluated a set of diploid <i>C. albicans</i> strains and found that a strain carrying a third copy of chromosome (Chr) 7 was associated with increased fitness during both gastrointestinal (GI) colonization and systemic infection. Our analysis revealed that the presence of a Chr 7 trisomy resulted in decreased filamentation, both in vitro and during GI colonization, relative to isogenic euploid controls. A target gene approach demonstrated that <i>NRG1</i>, encoding a negative regulator of filamentation located on Chr 7, contributes to increased fitness of the aneuploid strain due to inhibition of filamentation in a gene dosage-dependent fashion. Together, these experiments establish how aneuploidy enables the reversible adaptation of <i>C. albicans</i> to its host via gene dosage-dependent regulation of morphology.