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dc.contributor.authorLesic, Biliana
dc.contributor.authorLépine, François
dc.contributor.authorDéziel, Eric
dc.contributor.authorZhang, Qunhao
dc.contributor.authorPadfield, Katie
dc.contributor.authorCastonguay, Marie-Hélène
dc.contributor.authorMilot, Sylvain
dc.contributor.authorStachel, Scott
dc.contributor.authorZhang, Jiangwen
dc.contributor.authorTzika, A. Aria
dc.contributor.authorTompkins, Ronald Gary
dc.contributor.authorRahme, Laurence G.
dc.date.accessioned2011-02-22T17:50:22Z
dc.date.issued2007
dc.identifier.citationLesic, Biliana, François Lépine, Eric Déziel, Jiangwen Zhang, Qunhao Zhang, Katie Padfield, Marie-Hélène Castonguay, et al. 2007. Inhibitors of pathogen intercellular signals as selective anti-infective compounds. PLoS Pathogens 3(9): e126.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4729255
dc.description.abstractLong-term antibiotic use generates pan-resistant super pathogens. Anti-infective compounds that selectively disrupt virulence pathways without affecting cell viability may be used to efficiently combat infections caused by these pathogens. A candidate target pathway is quorum sensing (QS), which many bacterial pathogens use to coordinately regulate virulence determinants. The Pseudomonas aeruginosa MvfR-dependent QS regulatory pathway controls the expression of key virulence genes; and is activated via the extracellular signals 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), whose syntheses depend on anthranilic acid (AA), the primary precursor of 4-hydroxy-2-alkylquinolines (HAQs). Here, we identified halogenated AA analogs that specifically inhibited HAQ biosynthesis and disrupted MvfR-dependent gene expression. These compounds restricted P. aeruginosa systemic dissemination and mortality in mice, without perturbing bacterial viability, and inhibited osmoprotection, a widespread bacterial function. These compounds provide a starting point for the design and development of selective anti-infectives that restrict human P. aeruginosa pathogenesis, and possibly other clinically significant pathogens.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.0030126en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323289/pdf/en_US
dash.licenseLAA
dc.subjectchemical biologyen_US
dc.subjectinfectious diseasesen_US
dc.subjectmicrobiologyen_US
dc.subjectin vitroen_US
dc.subjectanimalsen_US
dc.subjectmus (mouse)en_US
dc.titleInhibitors of Pathogen Intercellular Signals as Selective Anti-Infective Compoundsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorTzika, A. Aria
dc.date.available2011-02-22T17:50:22Z
dash.affiliation.otherHMS^Surgery-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Surgery-Massachusetts General Hospitalen_US
dc.identifier.doi10.1371/journal.ppat.0030126*
dash.authorsorderedfalse
dash.contributor.affiliatedZhang, Jiangwen
dash.contributor.affiliatedTzika, A.
dash.contributor.affiliatedTompkins, Ronald
dash.contributor.affiliatedRahme, Laurence


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