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dc.contributor.advisor Bennett, George N.
dc.creatorLynn, Jed
dc.date.accessioned 2013-07-24T19:37:29Z
dc.date.accessioned 2013-07-24T19:37:31Z
dc.date.available 2013-07-24T19:37:29Z
dc.date.available 2013-07-24T19:37:31Z
dc.date.created 2012-12
dc.date.issued 2013-07-24
dc.date.submitted December 2012
dc.identifier.citation Lynn, Jed. "Anticipation of Nitric Oxide Stress in the Human Commensal Fungus Candida albicans." (2013) Diss., Rice University. http://hdl.handle.net/1911/71672.
dc.identifier.urihttp://hdl.handle.net/1911/71672
dc.description.abstract Candida 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectCandida albicans
Nitric oxide
Stress anticipation
Transcription
Flavohemoglobin
YHB1
CTA4
Molecular biology
dc.title Anticipation of Nitric Oxide Stress in the Human Commensal Fungus Candida albicans
dc.contributor.committeeMember Braam, Janet
dc.contributor.committeeMember Segatori, Laura
dc.contributor.committeeMember Stewart, Charles R.
dc.date.updated 2013-07-24T19:37:31Z
dc.identifier.slug 123456789/ETD-2012-12-280
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Biochemistry and Cell Biology
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy


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