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The peptide chain release factor methyltransferase PrmC is essential for pathogenicity and environmental adaptation of Pseudomonas aeruginosa PA14

Authors

  • Christian Pustelny,

    Corresponding author
    1. Institute of Molecular Bacteriology, Twincore, Center for Clinical and Experimental Infection Research, a joint venture of the Helmholtz Center of Infection Research and the Hannover Medical School, Hannover, Germany
    • Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany
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    • The first two authors made an equal contribution to the work.
  • Stephan Brouwer,

    1. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany
    2. Institute of Molecular Bacteriology, Twincore, Center for Clinical and Experimental Infection Research, a joint venture of the Helmholtz Center of Infection Research and the Hannover Medical School, Hannover, Germany
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    • The first two authors made an equal contribution to the work.
  • Mathias Müsken,

    1. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany
    2. Institute of Molecular Bacteriology, Twincore, Center for Clinical and Experimental Infection Research, a joint venture of the Helmholtz Center of Infection Research and the Hannover Medical School, Hannover, Germany
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  • Agata Bielecka,

    1. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany
    2. Institute of Molecular Bacteriology, Twincore, Center for Clinical and Experimental Infection Research, a joint venture of the Helmholtz Center of Infection Research and the Hannover Medical School, Hannover, Germany
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  • Andreas Dötsch,

    1. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany
    2. Institute of Molecular Bacteriology, Twincore, Center for Clinical and Experimental Infection Research, a joint venture of the Helmholtz Center of Infection Research and the Hannover Medical School, Hannover, Germany
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  • Manfred Nimtz,

    1. Cellular Proteome Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
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  • Susanne Häussler

    1. Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany
    2. Institute of Molecular Bacteriology, Twincore, Center for Clinical and Experimental Infection Research, a joint venture of the Helmholtz Center of Infection Research and the Hannover Medical School, Hannover, Germany
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For correspondence. E-mail Christian.pustelny@helmholtz-hzi.de; Tel. (+49) 53161813152; Fax (+49) 53161813099.

Summary

Pseudomonas aeruginosa pathogenicity and its capability to adapt to multiple environments are dependent on the production of diverse virulence factors, controlled by the sophisticated quorum sensing (QS) network of P. aeruginosa. To better understand the molecular mechanisms that underlie this adaptation we searched for novel key regulators of virulence factor production by screening a PA14 transposon mutant library for potential candidates acting downstream of the unique 2-alkyl-4-quinolone (AQ) QS system of P. aeruginosa. We focused the work on a protein named HemK with high homology to PrmC of Escherichia coli displaying a similar enzymatic activity (therefore also referred to as PrmC). In this study, we demonstrate that PrmC is an S-adenosyl-l-methionine (AdoMet)-dependent methyltransferase of peptide chain release factors (RFs) essential for the expression of several virulence factors, such as pyocyanin, rhamnolipids and the type III-secreted toxin ExoT. Furthermore, the PA14_prmC mutant strain is unable to grow under anoxic conditions and has a significantly reduced pathogenicity in the infection model Galleria mellonella. Along with transcriptomic and proteomic analyses, the presented data indicate that the methylation of RFs in P. aeruginosa seems to have a global effect on cellular processes related to the virulence of this nosocomial pathogen.

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