Anticipation of Nitric Oxide Stress in the Human Commensal Fungus Candida albicans

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dc.contributor.advisorBennett, George N.en_US
dc.contributor.committeeMemberBraam, Janeten_US
dc.contributor.committeeMemberSegatori, Lauraen_US
dc.contributor.committeeMemberStewart, Charles R.en_US
dc.creatorLynn, Jeden_US
dc.date.accessioned2013-07-24T19:37:29Zen_US
dc.date.accessioned2013-07-24T19:37:31Zen_US
dc.date.available2013-07-24T19:37:29Zen_US
dc.date.available2013-07-24T19:37:31Zen_US
dc.date.created2012-12en_US
dc.date.issued2013-07-24en_US
dc.date.submittedDecember 2012en_US
dc.date.updated2013-07-24T19:37:31Zen_US
dc.description.abstractCandida albicans is the most common human commensal fungus, able to colonize host niches such as skin, mouth and gastrointestinal tract. Colonization of diverse microenvironments requires the ability to evade or overcome innate host protection and adapt to rapid transitions between environments with different stresses and nutrient availability. Colonization of the gastrointestinal tract requires passage through the stomach containing toxic levels of nitric oxide, generated from acidification of nitrite in the low pH of the stomach. Although resistance of C. albicans to nitric oxide is mediated by the flavohemoglobin Yhb1, little is known about the physiologically relevant ligands that regulate YHB1 expression. Here I propose the hypothesis that nontoxic saliva chemicals induce YHB1 expression and promote resistance to nitric oxide generated in the stomach. Supporting this hypothesis is the observation that two ions actively concentrated in the saliva – nitrate and thiocyanate – induce YHB1 expression. Indeed, whole-genome transcriptional analysis of C. albicans treated with nitrate or thiocyanate produce gene expression profiles nearly identical to cells treated with nitrite or nitric oxide. Pretreatment of C. albicans with either of these two nontoxic compounds increases resistance of the yeast to nitric oxide. I propose that this is an evolved response in which C. albicans anticipates nitric oxide stress generated in the stomach. C. albicans thus upregulates nitric oxide stress response genes in response to saliva signals that precede nitric oxide formation further on in the gut. Only a few examples of anticipatory signaling have so far been identified and it is not known how common this type of regulation is among microbes. Expression of the YHB1 gene in response to nitric oxide is regulated by the transcription factor Cta4. I show that Cta4 binds to the YHB1 promoter in vivo as a homodimer and is necessary, but not sufficient, for nitric oxide, nitrate and thiocyanate induced expression of YHB1. Based on these data I propose a model in which Cta4 transcriptional activation is inhibited under non-inducing conditions by a negative regulator. Understanding the mechanism by which C. albicans senses and responds to nitric oxide, nitrate and thiocyanate remains a question for future research.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationLynn, Jed. "Anticipation of Nitric Oxide Stress in the Human Commensal Fungus Candida albicans." (2013) Diss., Rice University. <a href="https://hdl.handle.net/1911/71672">https://hdl.handle.net/1911/71672</a>.en_US
dc.identifier.slug123456789/ETD-2012-12-280en_US
dc.identifier.urihttps://hdl.handle.net/1911/71672en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectCandida albicansen_US
dc.subjectNitric oxideen_US
dc.subjectStress anticipationen_US
dc.subjectTranscriptionen_US
dc.subjectFlavohemoglobinen_US
dc.subjectYHB1en_US
dc.subjectCTA4en_US
dc.subjectMolecular biologyen_US
dc.titleAnticipation of Nitric Oxide Stress in the Human Commensal Fungus Candida albicansen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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