Insights into the molecular mechanisms of sensing and responding to the host by Staphylococcus aureus

dc.contributor.advisorChairperson, Graduate Committee: Jovanka Voyich-Kaneen
dc.contributor.authorMeishery-Patel, Delishaen
dc.contributor.otherK. B. Pallister and Jovanka Voyich were co-authors of the article, 'Role of SaeR phosphorylation in regulation of Staphylococcus aureus virulence genes' which is contained within this thesis.en
dc.contributor.otherDissertation contains an article of which Delisha Meishery-Patel is not the main author.en
dc.description.abstractTwo-component systems (TCSs) are highly conserved across bacteria and are used to rapidly sense and respond to changing environmental conditions. The human pathogen Staphylococcus aureus uses the S. aureus exoprotein expression (sae) TCS to sense host signals and activate transcription of virulence factors essential to pathogenesis. Despite its importance, the mechanism by which the sensor kinase (SaeS) recognizes a stimulus and activates its cognate response regulator (SaeR) to regulate transcription of virulence genes is incompletely defined. However, findings from our lab suggest that SaeR/S mediated transcription is unique-to and dependent-on specific host stimuli. Studies outlined in this dissertation suggest that residues in the extracellular loop may be involved in refinement of the sae regulated targets at the single amino acid level. By generating single amino acid replacement mutants in the response regulator SaeR, we identified a key aspartate residue at position 46 (D46) on SaeR to be important in SaeR mediated signaling as mutation D46A prevented the recombinant protein from binding promoter recognition sequence and subsequently influenced virulence regulation. Current studies are aimed to define the phosphorylation patterns in SaeR using SDS-PAGE analysis and mass spectrometry. Overall, these structure-function studies provide insight into the Sae- signal transduction mechanism and raise some new questions regarding the role the Sae system in the larger regulatory network S. aureus uses to control expression of its secreted virulence factors.en
dc.publisherMontana State University - Bozeman, College of Agricultureen
dc.rights.holderCopyright 2018 by Delisha Meishery-Patelen
dc.subject.lcshStaphylococcus aureusen
dc.subject.lcshGene expressionen
dc.subject.lcshNatural immunityen
dc.titleInsights into the molecular mechanisms of sensing and responding to the host by Staphylococcus aureusen
dc.typeDissertationen, Graduate Committee: Mark T. Quinn; Michael Franklin; Brian Bothner.en & Immunology.en


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