Characterizing the Role of the E. Coli Cytochrome Oxidase AppBCX During Intestinal Inflammation

dc.contributor.advisorSperandio, Vanessaen
dc.contributor.committeeMemberWinter, Sebastian E.en
dc.contributor.committeeMemberPfeiffer, Julie K.en
dc.contributor.committeeMemberMoreland, Jessicaen
dc.creatorChanin, Rachael Bethen
dc.creator.orcid0000-0002-4625-356X
dc.date.accessioned2023-09-14T22:28:12Z
dc.date.available2023-09-14T22:28:12Z
dc.date.created2021-08
dc.date.issuedAugust 2021
dc.date.submittedAugust 2021
dc.date.updated2023-09-14T22:28:12Z
dc.description.abstractDuring non-infectious colitis, oral antibiotic treatment, and enteric infection, changes in colonocyte metabolism allow for increased oxygen availability in the gut lumen, supporting the growth of facultative anaerobic bacteria primarily from the family Enterobacteriaceae. Additionally, recruitment of inflammatory cells, especially neutrophils, has also been shown to influence local oxygen levels. The oxidative burst mounted by neutrophils consumes oxygen, which in turn creates a hyper-hypoxic microenvironment. These two seemingly contradictory findings remain to be reconciled. The findings described here delineate an additional mechanism that helps explain these seemingly contradictory observations on oxygen availability and bacterial respiratory processes during non-infectious colitis. The picture emerging from our work is that reactive oxygen species (ROS) generated by the NADPH oxidase 1 (NOX1) at the epithelial interface serve as a local source of oxygen. Specifically, H2O2 deriving from epithelial NOX1, is detoxified via bacterial catalases to molecular oxygen. Facultative anaerobic bacteria can then respire this pool of oxygen. In this work, we have used commensal strains of E. coli as representative members of Enterobacteriaceae, a family of facultative anaerobic bacteria that is observed to outgrow during episodes of inflammation. In particular, we have studied the physiological function of the cytochrome bd oxidase, AppBCX. Using both chemical and genetic models of non-infectious colitis we have shown that it allows E. coli to utilize low levels of oxygen early in inflammation. Additionally, we have characterized the regulation of this enzyme in vivo highlighting the delicate balance between growth and survival during oxidative and nitrosative stress.en
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttps://hdl.handle.net/2152.5/10184
dc.language.isoenen
dc.subjectElectron Transport Complex IVen
dc.subjectEscherichia colien
dc.subjectInflammationen
dc.subjectIntestinal Mucosaen
dc.subjectNADPH Oxidase 1en
dc.subjectReactive Oxygen Speciesen
dc.titleCharacterizing the Role of the E. Coli Cytochrome Oxidase AppBCX During Intestinal Inflammationen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineMolecular Microbiologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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