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MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands

Xiao, Gaoping; Déziel, Éric; He, Jianxin; Lépine, François; Lesic, Biliana; Castonguay, Marie-Hélène; Milot, Sylvain; Tampakaki, Anastasia P; Stachel, Scott; Rahme, Laurence G. (2006). MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands Molecular Microbiology , vol. 62 , nº 6. p. 1689-1699. DOI: 10.1111/j.1365-2958.2006.05462.x.

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Résumé

MvfR (PqsR), a Pseudomonas aeruginosa LysR-type transcriptional regulator, plays a critical role in the virulence of this pathogen. MvfR modulates the expression of multiple quorum sensing (QS)-regulated virulence factors; and the expression of the phnAB and pqsA-E genes that encode functions mediating 4-hydroxy-2-alkylquinolines (HAQs) signalling compounds biosynthesis, including 3,4-dihydroxy-2-heptylquinoline (PQS) and its precursor 4-hydroxy-2- heptylquinoline (HHQ). PQS enhances the in vitro DNA-binding affinity of MvfR to the pqsA-E promoter, to suggest it might function as the in vivo MvfR ligand. Here we identify a novel MvfR ligand, as we show that HHQ binds to the MvfR ligand-binding-domain and potentiates MvfR binding to the pqsA-E promoter leading to transcriptional activation of pqsA-E genes. We show that HHQ is highly produced in vivo, where it is not fully converted into PQS, and demonstrate that it is required for MvfR-dependent gene expression and pathogenicity; PQS is fully dispensable, as pqsH- mutant cells, which produce HHQ but completely lack PQS, display normal MvfR-dependent gene expression and virulence. Conversely, PQS is required for full production of pyocyanin. These results uncover a novel biological role for HHQ; and provide novel insights on MvfR activation that may aid in the development of therapies that prevent or treat P. aeruginosa infections in humans

Type de document:
Mots-clés libres: QUORUM-SENSING CIRCUITRY, TO-CELL COMMUNICATION, CAENORHABDITIS ELEGANS, VIRULENCE FACTORS, QUINOLONE SIGNAL, LYSR FAMILY, GENES, PATHOGENESIS, INFECTION, FRAGMENT
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 01 mai 2014 18:49
Dernière modification: 01 mai 2014 18:49
URI: http://espace.inrs.ca/id/eprint/2234

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