Rbt1 is required for Nitric Oxide Stress Resistance in the Human Commensal Fungus Candida albicans
Gustin, Michael C.
Master of Arts
Candida albicans is a human‐resident opportunistic fungal pathogen. Persistence of C. albicans is largely affected by resistance to host‐generate nitric oxide (NO) mediated nitrosative stress. The transcription factor Cta4 was first identified by our group as a regulator of the nitrosative stress resistance gene YHB1. However, little else is known about the molecular mechanism of C. albicans resistance to NO. Here I propose that there are proteins besides Cta4 involved in the regulation of C. albicans nitrosative stress resistance and Rbt1 is one of the positive regulators. Supporting this hypothesis is the observation that Δrbt1 showed significantly inhibited growth when challenged with nitrosative stress producing chemicals nitrite and DPTA Nonoate. Quantitative PCR showed that YHB1 was no longer transcriptionally induced by nitric oxide compared to the wild type strain. Complementation with the plasmid expressing RBT1 gene is needed to confirm the function of Rbt1. But the fact that Δrbt1 mutants generated by other labs showed the same phenotype supported our observation. The screening assay indicated in this thesis yielded several mutants with significant sodium nitrite sensitivity and this suggests that multiple Candida albicans proteins might function synergistically to detoxify in vivo nitric oxide.