Sensitivity of White and Opaque Candida albicans Cells to Antifungal Drugs.
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ABSTRACT:
SUBMITTER: Craik VB
PROVIDER: S-EPMC5527646 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
Sensitivity of White and Opaque Candida albicans Cells to Antifungal Drugs.
Craik Veronica B VB Johnson Alexander D AD Lohse Matthew B MB
Antimicrobial agents and chemotherapy 20170725 8
White and opaque cells of <i>Candida albicans</i> have the same genome but differ in gene expression patterns, metabolic profiles, and host niche preferences. We tested whether these differences, which include the differential expression of drug transporters, resulted in different sensitivities to 27 antifungal agents. The analysis was performed in two different strain backgrounds; although there was strain-to-strain variation, only terbinafine hydrochloride and caspofungin showed consistent, 2- ...[more]
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Project description:The human fungal pathogen Candida albicans can switch between two phenotypic cell types, termed 'white' and 'opaque'. Both cell types are heritable for many generations, and the switch between the two types occurs epigenetically, that is, without a change in the primary DNA sequence of the genome. Previous work identified six key transcriptional regulators important for white-opaque switching: Wor1, Wor2, Wor3, Czf1, Efg1, and Ahr1. In this work, we describe the structure of the transcriptional network that specifies the white and opaque cell types and governs the ability to switch between them. In particular, we use a combination of genome-wide chromatin immunoprecipitation, gene expression profiling, and microfluidics-based DNA binding experiments to determine the direct and indirect regulatory interactions that form the switch network. The six regulators are arranged together in a complex, interlocking network with many seemingly redundant and overlapping connections. We propose that the structure (or topology) of this network is responsible for the epigenetic maintenance of the white and opaque states, the switching between them, and the specialized properties of each state.
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