ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model

Abstract

Gastrointestinal colonization by <i>Candida</i> species is considered the main source of candidemia. The <i>ERG3</i> gene in <i>Candida albicans</i> encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although <i>ERG3</i> inactivation shows reduced virulence in mouse models of disseminated candidiasis, the role of <i>ERG3</i> in intestinal infections is unknown. Here, we infected mice with the <i>C. albicans</i> strains CAE3DU3 and CAF2-1, containing mutant and wild-type <i>ERG3</i>, respectively, and studied gut infection and colonization by these strains. We found that the CAE3DU3 strain showed reduced colonization, pathogenesis, damage to gut mucosa, and chemokine production in the mouse model of invasive candidiasis. Additionally, mice inoculated with CAE3DU3 showed lower mortality than mice inoculated with CAF2-1 (<i>p</i> < 0.0001). Chemokines were less induced in the gut inoculated with CAE3DU3 than in the gut inoculated with CAF2-1. Histopathologically, although the wild-type gene was associated with a higher pathogenicity and invasion of the gut mucosa and liver tissues causing remarkable tissue necrosis, the <i>erg3</i>/<i>erg3</i> mutant was associated with a higher accumulation of cells and lower damage to surrounding tissues than wild-type <i>ERG3</i>. These results establish that the ergosterol biosynthetic pathway may be associated with <i>C. albicans</i> gut colonization and subsequent dissemination.