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003 OCoLC;

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008 150901s2015 ncua ob 000 0 eng d;

035 a| (Sirsi) o919514665;

035 a| (OCoLC)919514665;

049 a| EREE;

100 1 a| Farrow, John M.,c| III,e| author.?| UNAUTHORIZED;

245 10 a| Transcriptional regulation of 'pqsR', a gene that encodes a regulator of quinolone signal synthesis and virulence in 'Pseudomonas aeruginosa' /c| by John M. Farrow, III.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2015.;

300 a| 123 pages :b| illustrations (some color);

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 3.52Mb2| rda;

490 1 a| ECU Brody School of Medicine thesis;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph.D.c| East Carolina Universityd| 2015.;

500 a| Presented to the faculty of the Department of Microbiology and Immunology.;

500 a| Advisor: Everett C. Pesci.;

500 a| Title from PDF t.p. (viewed August 28, 2015).;

520 3 a| The 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.;

504 a| Includes bibliographical references.;

650 2 a| Cystic Fibrosis.=| ^A919318;

650 2 a| Gene Expression Regulation, Bacterialx| physiology.=| ^A1273102;

650 2 a| Quinolonesx| metabolism.=| ^A1260949;

650 2 a| Transcription, Geneticx| physiology.=| ^A1273095;

653 a| Microbiology;

653 a| 4-hydroxy-2-alkylquinolones;

653 a| CysB;

653 a| Cysteine;

653 a| PQS;

653 a| Pseudomonas Aeruginosa;

700 1 a| Pesci, Everett C.,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Microbiology and Immunology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine thesis.=| ^A964744;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/4990;

949 o| jdjr;

994 a| C0b| ERE;

096 a| QW 131;

596 a| 1 4;

998 a| 3808264;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 3808264-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 9/1/2015x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 3808264-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 9/1/2015x| ETDz| HERESOURCE;

Transcriptional regulation of 'pqsR', a gene that encodes a regulator of quinolone signal synthesis and virulence in 'Pseudomonas aeruginosa' / by John M. Farrow, III.

Author/creator	Farrow, John M. author.
Other author	Pesci, Everett C., degree supervisor.
Other author	East Carolina University. Department of Microbiology and Immunology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2015.
Description	123 pages : illustrations (some color)
Supplemental Content	Access via ScholarShip
Subjects	Cystic Fibrosis. Gene Expression Regulation, Bacterial--physiology. Quinolones--metabolism. Transcription, Genetic--physiology.

Series	ECU Brody School of Medicine thesis ECU Brody School of Medicine thesis. ^A964744
Summary	The 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.
General note	Presented to the faculty of the Department of Microbiology and Immunology.
General note	Advisor: Everett C. Pesci.
General note	Title from PDF t.p. (viewed August 28, 2015).
Dissertation note	Ph.D. East Carolina University 2015.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Transcriptional regulation of 'pqsR', a gene that encodes a regulator of quinolone signal synthesis and virulence in 'Pseudomonas aeruginosa' / by John M. Farrow, III.

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