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Links and regulatory loops between phospholipase C activity and colonization by the O2-responsive regulator Anr in Pseudomonas aeruginosa / by Angelyca A. Jackson.

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Author	Jackson, Angelyca A.
Title	Links and regulatory loops between phospholipase C activity and colonization by the O2-responsive regulator Anr in Pseudomonas aeruginosa / by Angelyca A. Jackson.
Date	2014
Abstract	Pseudomonas aeruginosa is a virulent opportunistic pathogen that is frequently cultured from infectious sites, and is estimated to cause ~12% of nosocomial infections worldwide [1]. P. aeruginosa infections occur in a majority of adults with the heritable disease cystic fibrosis (CF), and its the primary agent of morbidity and mortality in CF patients because it contributes to increased exacerbation frequency and decreased lung function [2-4]. Its role in lung function decline is attributable to its expansive array of virulence factors and persistence within the host due at least in part to growth in biofilms, which are cell aggregates encased in an aqueous matrix. This thesis establishes a central role for the oxygen-sensitive transcription factor Anr in biofilm formation and host colonization in P. aeruginosa. Catabolism of the phospholipid phosphatidylcholine (PC) is demonstrated to stimulate biofilm development through activation of Anr by a mechanism that remains unknown. It is clear, however, that choline oxidation is required for this effect. A microarray experiment in medium with PC revealed that in comparison to strains unable to catabolize PC, the most highly upregulated transcripts in PAO1 WT were genes that remain uncharacterized, but feature Anr consensus sequences in their promoters. We show that Anr is required for normal biofilm development and host colonization at early time points indicating that Anr promotes colonization during the acute phase of infection. Known Anr targets are not required for the stimulation of biofilm formation, suggesting clinically relevant roles for the uncharacterized genes that are suspected to be Anr regulated. Data is also presented implicates a role for Anr in chronic infection establishment by repression of hemolytic phospholipase C, PlcH. When oxygen levels are low, Anr represses plcH by binding to its consensus sequence in the plcH promoter. Anr overexpression is shown to be sufficient for plcH repression. This regulation is presumably due to the fact that the choline and fatty acids released from PC require oxygen for oxidation. These findings further expand the role of Anr in P. aeruginosa beyond strict regulation of microaerobic and anaerobic respiration and demonstrate its importance in clinically relevant group behaviors.
Description	xii, 231 leaves : ill. (some col.)
Format	application/pdf
College	Dartmouth Medical School. Department of Microbiology and Immunology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1240

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Links and regulatory loops between phospholipase C activity and colonization by the O2-responsive regulator Anr in Pseudomonas aeruginosa / by Angelyca A. Jackson.

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