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Cross-kingdom communication: The role of quorum sensing signals in Candida albicans and Pseudomonas aeruginosa interactions.

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Call No.	Ph.D. 2010
Author	Cugini, Carla.
Title	Cross-kingdom communication: The role of quorum sensing signals in Candida albicans and Pseudomonas aeruginosa interactions.
Date	2010
Abstract	The overall scope of my thesis project is to determine effects of farnesol, a secreted factor produced by C. albicans , on P. aeruginosa virulence. These two organisms are frequently found with one another in mixed infections and our lab has previously determined that they affect each other in numerous ways. I have found that farnesol, a secreted factor produced by C. albicans , can decrease virulence factor regulation in P. aeruginosa, by interacting with PqsR, a global virulence factor regulator. P. aeruginosa clinical isolates can be divided into a number of different classes (phenotypic and genetic) based on acquired heritable mutations. In a subset of strains isolated from Cystic Fibrosis (CF) patients, I have found that farnesol increases virulence factor production. This subset shares a common loss-of-function mutation in the LasR transcriptional regulator, and when grown in the presence of farnesol, there is an increase in the production of PQS, a key virulence factor regulator. We have been able to confirm the phenotype using a non-polar PA14? lasR mutant. Using the non-polar lasR mutant, it was demonstrated that the increase in PQS production by farnesol is due to the upregulation of pqsH transcription, which is dependent on RhlR and the canonical PQS biosynthetic and regulatory pathway. The increase in PQS production can be inhibited by the addition of an oxidative stress protectant, suggesting that farnesol is inducing oxidative stress in the bacterium. The work presented here examines the complex multispecies interaction, with the attempt to characterize the interaction at the molecular and mechanistic level, which when understood can aid in the development of better treatments for P. aeruginosa or C. albicans infections
Description	xi, 235 leaves : ill. (some col.) ; 28 cm.
Format	application/pdf
Advisor	Guerinot, Mary Lou, Sundstrom, Paula, Pesci, Everett, Hogan, Deborah A.
Subject	Pseudomonas aeruginosa -- Molecular genetics. Candida albicans. Pseudomonas aeruginosa infections. Plant-pathogen relationships. Cystic fibrosis -- Immunological aspects. Virulence (Microbiology) -- Molecular aspects. Medical Terms: Farnesol; Virulence Factors; Quorum Sensing.
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.387

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Cross-kingdom communication: the role of quorum sensing signals in Candida albicans and Pseudomonas aeruginosa interactions A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Microbiology and Immunology by Carla Cugini DARTMOUTH COLLEGE Hanover, New Hampshire January 2010 Examining Committee: Deborah Hogan (chair) Mary Lou Guerinot Paula Sundstrom Brian W. Pogue, Ph.D. Everett Pesci Dean of Graduate Studies

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