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

Candida albicans is an efficient colonizer of human gastrointestinal tracts and skin and is an opportunistic pathogen. C. albicans exhibits 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 by C. albicans throughout growth. However, the synthesis, secretion, regulation, and turnover of farnesol is not fully understood. To address this, we used our improved farnesol assay to screen a transcription regulator knockout library of 164 mutants for farnesol accumulation in whole cultures, pellets, and supernatants. All mutants produced farnesol and they averaged 9.2X more farnesol in the pellet than the supernatant. Nineteen mutants had significant differences with ten mutants producing more farnesol than their SN152+ parent while nine produced less. Seven mutants exhibited greater secretion of farnesol while two exhibited less. We examined the time course for farnesol accumulation in six mutants with the greatest accumulation differences and found that those differences persisted throughout growth and they were not time dependent. Significantly, two high accumulating mutants did not exhibit the decay in farnesol levels during stationary phase characteristic of wild type C. albicans, suggesting that a farnesol modification/degradation mechanism is absent in these mutants. Identifying these transcriptional regulators provides new insight into farnesols physiological functions regarding cell cycle progression, white-opaque switching, yeast-mycelial dimorphism, and response to cellular stress.