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The global regulator Crc modulates metabolism, susceptibility to antibiotics and virulence in Pseudomonas aeruginosa

Authors

  • Juan F. Linares,

    1. Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
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    • Present address: Vontz Center for Molecular Studies, Department of Cancer and Cell Biology, University of Cincinnati Medical Center, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.

    • The first two authors contributed equally to this work.

  • Renata Moreno,

    1. Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
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    • The first two authors contributed equally to this work.

  • Alicia Fajardo,

    1. Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
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  • Laura Martínez-Solano,

    1. Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
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  • Ricardo Escalante,

    1. Instituto de Investigaciones Biomédicas Alberto Sols, UAM-CSIC, Madrid, Spain.
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  • Fernando Rojo,

    1. Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
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  • José L. Martínez

    Corresponding author
    1. Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
    2. CIBERESP, Madrid, Spain.
      E-mail jlmtnez@cnb.csic.es; Tel. (+34) 91 5854542; Fax (+34) 91 5854506.
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E-mail jlmtnez@cnb.csic.es; Tel. (+34) 91 5854542; Fax (+34) 91 5854506.

Summary

The capacity of a bacterial pathogen to produce a disease in a treated host depends on the former's virulence and resistance to antibiotics. Several scattered pieces of evidence suggest that these two characteristics can be influenced by bacterial metabolism. This potential relationship is particularly important upon infection of a host, a situation that demands bacteria adapt their physiology to their new environment, making use of newly available nutrients. To explore the potential cross-talk between bacterial metabolism, antibiotic resistance and virulence, a Pseudomonas aeruginosa model was used. This species is an important opportunistic pathogen intrinsically resistant to many antibiotics. The role of Crc, a global regulator that controls the metabolism of carbon sources and catabolite repression in Pseudomonas, was analysed to determine its contribution to the intrinsic antibiotic resistance and virulence of P. aeruginosa. Using proteomic analyses, high-throughput metabolic tests and functional assays, the present work shows the virulence and antibiotic resistance of this pathogen to be linked to its physiology, and to be under the control (directly or indirectly) of Crc. A P. aeruginosa strain lacking the Crc regulator showed defects in type III secretion, motility, expression of quorum sensing-regulated virulence factors, and was less virulent in a Dictyostelium discoideum model. In addition, this mutant strain was more susceptible to beta-lactams, aminoglycosides, fosfomycin and rifampin. Crc might therefore be a good target in the search for new antibiotics.

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