The CTA4 transcription factor mediates induction of nitrosative stress response in the fungal pathogen Candida albicans

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dc.contributor.advisorGustin, Michael C.en_US
dc.creatorChiranand, Wiriyaen_US
dc.date.accessioned2009-06-03T21:05:55Zen_US
dc.date.available2009-06-03T21:05:55Zen_US
dc.date.issued2007en_US
dc.description.abstractI have identified regulatory elements in the pathogen Candida albicans that enable response to nitrosative stress. This dimorphic fungus typically resides in the digestive and genitourinary tracts as an innocuous constituent of the normal microflora but can opportunistically cause superficial mucosal infection. In immunocompromised patients, such infections may also progress to potentially lethal systemic disease. One adaptation that facilitates survival of C. albicans against the hostile environment inside the mammalian body is the ability to resist toxic reactive nitrogen species (RNS) generated by macrophages of the host immune system. Recent studies have shown that exposing C. albicans to nitric oxide, one type of RNS, induces upregulation of the flavohemoglobin Yhb1p. This protein confers protection by enzymatically converting nitric oxide to harmless nitrate, but it is unknown how C. albicans is able to detect nitric oxide in its environment and thus initiate this defense only as needed. I therefore analyzed this problem by incrementally mutating the YHB1 regulatory region to identify a nitric oxide-responsive element (NORE) that is required for NO sensitivity. Five transcription factor candidates of the Zn(II)2-Cys6 family were then isolated by using magnetic beads coated with this DNA element in crude whole cell extracts. Of the five, only deletion of the CTA4 gene prevented induction of YHB1 transcription during nitrosative stress and caused growth sensitivity to the nitric oxide donor DPTA NONOate. The virulence of the cta4Delta deletion mutant was also mildly impaired, slightly more so than that of a yhb1Delta deletion mutant. Cta4p is the first protein found to be necessary for nitric oxide response in C. albicans .en_US
dc.format.extent120 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS BIOCHEM. 2007 CHIRANANDen_US
dc.identifier.citationChiranand, Wiriya. "The CTA4 transcription factor mediates induction of nitrosative stress response in the fungal pathogen Candida albicans." (2007) Diss., Rice University. <a href="https://hdl.handle.net/1911/20588">https://hdl.handle.net/1911/20588</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/20588en_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.subjectMolecular biologyen_US
dc.titleThe CTA4 transcription factor mediates induction of nitrosative stress response in the fungal pathogen 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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