Transcriptional regulation of 'pqsR', a gene that encodes a regulator of quinolone signal synthesis and virulence in 'Pseudomonas aeruginosa'

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dc.contributor.advisorPesci, Everett C.
dc.contributor.authorFarrow, John M. III
dc.contributor.departmentMicrobiology and Immunology
dc.date.accessioned2015-08-24T16:23:40Z
dc.date.available2017-02-07T22:22:33Z
dc.date.issued2015
dc.description.abstractThe gram-negative bacterium 'Pseudomonas aeruginosa' is an opportunistic pathogen that frequently causes nosocomial infections and serious chronic lung infections in cystic fibrosis patients. During infection 'P. aeruginosa' communicates through multiple cell-to-cell signaling molecules to coordinate the expression of numerous virulence determinants. The production of these signaling molecules forms a regulatory network, with the signal N-(3-oxododecanoyl) homoserine lactone and its receptor LasR controlling the induction of a second homoserine lactone signal and the 'Pseudomonas' quinolone signal (PQS). LasR-mediated control of PQS occurs partly through the activation of 'pqsR', a gene that encodes the PQS receptor and is necessary for PQS production. We demonstrate that LasR induces 'pqsR' expression by interacting with a single binding site in the 'pqsR' promoter region that is distant from the 'pqsR' translational start site. Through a search for additional factors that control 'pqsR' expression we found that the transcriptional regulator CysB competes with LasR for binding to the 'pqsR' promoter, and that it negatively affects 'pqsR' expression and PQS production. However, unlike other CysB-controlled genes, 'pqsR' was not differentially regulated in response to cysteine levels. We also show that LasR activates 'pqsR' transcription at a distal promoter site, but other sequences in the 'pqsR' promoter region constitute a negative regulatory element that limits 'pqsR' expression. These findings show that the transcription of 'pqsR', and subsequently PQS production, is controlled by the interplay of both positive and negative regulatory mechanisms. Finding ways to manipulate these regulatory pathways could be a potential strategy to combat 'P. aeruginosa' virulence.
dc.description.degreePh.D.
dc.format.extent123 p.
dc.format.mediumdissertations, academic
dc.identifier.urihttp://hdl.handle.net/10342/4990
dc.publisherEast Carolina University
dc.subjectMicrobiology
dc.subject4-hydroxy-2-alkylquinolones
dc.subjectCysB
dc.subjectCysteine
dc.subjectPQS
dc.subjectPseudomonas aeruginosa
dc.subject.meshCystic Fibrosis
dc.subject.meshGene expression Regulation, Bacterial--physiology
dc.subject.meshQuinolones--metabolism
dc.subject.meshTranscription, Genetic-- physiology
dc.titleTranscriptional regulation of 'pqsR', a gene that encodes a regulator of quinolone signal synthesis and virulence in 'Pseudomonas aeruginosa'
dc.typeDoctoral Dissertation

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