The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: multiple quorum sensing-regulated genes are modulated without affecting lasRI, rhlRI or the production of N-acyl- l-homoserine lactones

Authors

  • Eric Déziel,

    1. Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 50 Blossom Street, and Shriners Burns Institute Boston, MA, USA.
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    • Present address: INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, Québec, Canada.

  • Suresh Gopalan,

    1. Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 50 Blossom Street, and Shriners Burns Institute Boston, MA, USA.
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  • Anastasia P. Tampakaki,

    1. Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 50 Blossom Street, and Shriners Burns Institute Boston, MA, USA.
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  • François Lépine,

    1. INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, Québec, Canada.
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  • Katie E. Padfield,

    1. Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 50 Blossom Street, and Shriners Burns Institute Boston, MA, USA.
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  • Maude Saucier,

    1. Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 50 Blossom Street, and Shriners Burns Institute Boston, MA, USA.
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  • Gaoping Xiao,

    1. Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 50 Blossom Street, and Shriners Burns Institute Boston, MA, USA.
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  • Laurence G. Rahme

    Corresponding author
    1. Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 50 Blossom Street, and Shriners Burns Institute Boston, MA, USA.
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Summary

The transcriptional regulator MvfR is required for full Pseudomonas aeruginosa virulence, the function of multiple quorum sensing (QS)-regulated virulence factors and the synthesis of 4-hydroxy-2-alkylquinolines (HAQs), including the Pseudomonas quinolone signal (PQS). Here we investigate the role of MvfR in the QS circuitry and P. aeruginosa pathogenesis. We demonstrate using a combination of biochemical and molecular approaches, including transcription profiling, that MvfR is involved in the regulation of multiple P. aeruginosa QS-controlled genes without altering the expression of lasRI/rhlRI or the production of N-acyl- l-homoserine lactone (AHL) signals. Dissection of how mvfR is interwoven into the P. aeruginosa QS circuitry reveals that the MvfR system, through the essential contribution of PqsE, positively regulates a subset of genes dependant on both LasR and RhlR. Animal studies show that MvfR contributes to P. aeruginosa virulence by controlling the transcription of genes not under RhlR regulation, and that reduced virulence of a mvfR mutant is caused by the loss of pqsE expression and not only a deficiency in HAQs/PQS production. This study provides novel insights into the unique role of the MvfR system in AHL-mediated QS and further supports its importance in P. aeruginosa pathogenesis.

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