Niche-activated defense mechanisms of a commensal fungus

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Humans and other animals are host to a variety of microbes. Different locations such as skin, mouth or digestive system have different communities of microbes. How microbes adapt to these locations and the special stresses there is not well understood. Indeed, adaptation to stress is a major factor in determining which microbes are on skin versus mouth, etc. A striking discovery is that the human-resident yeast Candida albicans senses nontoxic components of saliva (nitrate, thiocyanate) and activates defenses against toxic chemicals (nitrite and nitric oxide) generated in the mouth and stomach. This finding suggests that microbes sense their local environment and then induce responses to allow more effective survival and growth in that host niche. To further test this novel hypothesis, components of the yeast signaling pathway that allow ?anticipation? of toxic nitrite/nitric oxide stress will be identified and characterized using genetics and biochemistry. Another goal is to investigate the molecular mechanisms used by Candida to sense and resist a toxic bleach-like chemical called hypothiocyanite that is produced naturally in the mouth. This grant will also initiate the Research Apprentice Mentoring Project wherein a minority student from a Houston public high school will conduct research each summer on Candida-host interaction and, importantly, communicate their research results and experience back to peers at the same high school, from which another student will be recruited for doing research and so on. Two important impacts of this grant are thus the investigations of an exciting new aspect stress anticipation of microbe-host interaction and a potentially transformative mechanism involving peer-to-peer communication - for engaging under-represented minority students in biology research.