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dc.contributor.authorHazan, Ronen N.
dc.contributor.authorHe, Jianxin
dc.contributor.authorXiao, Gaoping
dc.contributor.authorDekimpe, Valérie
dc.contributor.authorApidianakis, Yiorgos
dc.contributor.authorLesic, Biliana
dc.contributor.authorAstrakas, Christos
dc.contributor.authorDéziel, Eric
dc.contributor.authorLépine, François
dc.contributor.authorRahme, Laurence G.
dc.date.accessioned2012-02-20T01:35:49Z
dc.date.issued2010
dc.identifier.citationHazan, Ronen, Jianxin He, Gaoping Xiao, Valérie Dekimpe, Yiorgos Apidianakis, Biliana Lesic, Christos Astrakas, Eric Déziel, François Lépine, and Laurence G. Rahme. 2010. Homeostatic interplay between bacterial cell-cell signaling and iron in virulence. PLoS Pathogens 6(3): e1000810.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8191183
dc.description.abstractPathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1000810en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837411/pdf/en_US
dash.licenseLAA
dc.titleHomeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulenceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorHazan, Ronen N.
dc.date.available2012-02-20T01:35:49Z
dash.affiliation.otherHMS^Surgery-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Surgery-Massachusetts General Hospitalen_US
dc.identifier.doi10.1371/journal.ppat.1000810*
dash.contributor.affiliatedHazan, Ronen N.
dash.contributor.affiliatedRahme, Laurence


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