Transcriptional regulation of the synthesis and secretion of farnesol in the fungusCandida albicans:Examination of the Homann transcription regulator knockout collection

Abstract

Candida albicansis an efficient colonizer of human gastrointestinal tracts and skin and is an opportunistic pathogen.C. albicansexhibits morphological plasticity and the ability to switch between yeast and filamentous morphologies is associated with virulence. One regulator of this switch is the quorum sensing molecule farnesol which is produced inC. albicanscells throughout growth. In addition, aromatic fusel alcohols accumulate inC. albicanssupernatants and are implicated in regulating morphogenesis. The synthesis, secretion, and turnover of these molecules is not fully understood. To address this, we used our improved assay for farnesol and aromatic fusel alcohol quantification of whole cultures, pellets, and supernatants, to screen a transcription regulator knockout library of 164 mutants for differences in farnesol and aromatic fusel alcohol accumulation and localization. We found that all mutants produced farnesol with an average of 9.2X more farnesol localizing to the pellet in most mutants. Nineteen mutants had significant differences in accumulation and nine differed in localization. Ten mutants produced more farnesol than their SN152+parent, while nine produced less. Seven mutants exhibited greater secretion of farnesol while two exhibited less. Several of these mutants have known roles in white/opaque switching and cell cycle progression such as the farnesol overproducing mutantsahr1andswi4. The aromatic fusel alcohols were similarly characterized by four over- and eleven under-producing mutants. Phenethyl alcohol and tryptophol accumulation were closely proportional to one another, but despite their structural similarity, phenethyl alcohol and tyrosol accumulation were often regulated differently.