Hgc1 Independence of Biofilm Hyphae in Candida albicans

Abstract

Biofilm and hypha formation are central to virulence of the fungal pathogen Candida albicans. The G1 cyclin gene <i>HGC1</i> is required for hypha formation under diverse <i>in vitro</i> and <i>in vivo</i> growth conditions. Hgc1 is required for disseminated infection and is a linchpin in the argument that hyphal morphogenesis itself is required for pathogenicity. We report here that <i>HGC1</i> is dispensable for hypha formation during biofilm formation both <i>in vitro</i>, under strong inducing conditions, and <i>in vivo</i>, in a mouse oropharyngeal candidiasis model. These findings are validated with two or more C. albicans isolates. Systematic screening of overexpressed cyclin genes indicates that <i>CCN1</i> and <i>CLN3</i> can compensate partially for Hgc1 function during biofilm growth. This conclusion is also supported by the severity of the <i>hgc1</i>Δ/Δ <i>ccn1</i>Δ/Δ double mutant biofilm defect. Our results suggest that hypha formation in biofilm is accomplished by combined action of multiple cyclins, not solely by Hgc1. <b>IMPORTANCE</b> The <i>HGC1</i> gene encodes a cyclin that is required for virulence of the fungal pathogen Candida albicans. It is required to produce the elongated hyphal filaments of free-living planktonic cells that are associated with virulence. Here, we show that <i>HGC1</i> is not required to produce hyphae in the alternative growth form of a biofilm community. We observe Hgc1-independent hyphae in two infection-relevant situations, biofilm growth <i>in vitro</i> and biofilm-like oropharyngeal infection. Our analysis suggests that hypha formation in the biofilm state reflects combined action of multiple cyclins.