Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts

Authors

  • Shalina Mahajan-Miklos,

    1. Microbia Inc., One Kendall Square Building 1400W, Suite 1418, Cambridge, MA 02139, USA.
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  • Laurence G. Rahme,

    1. Department of Surgery, Harvard Medical School and Shriner's Burns Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
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  • Frederick M. Ausubel

    Corresponding author
    1. Department of Genetics, Harvard Medical School, and Wellman 10, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
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Abstract

Several strains of the human opportunistic pathogen Pseudomonas aeruginosa infect plants, nematodes and insects. Our laboratory has developed a multihost pathogenesis system based on the P. aeruginosa clinical isolate PA14, in which non-mammalian hosts are used to screen directly for virulence-attenuated mutants. The majority of PA14 mutants isolated using non-mammalian hosts also displayed reduced virulence in a burned mouse model. Surprisingly, only a few host-specific virulence factors were identified, and many of the P. aeruginosa mutants were attenuated in virulence in all the hosts. These studies illustrate the extensive conservation in the virulence mechanisms used by P. aeruginosa to infect evolutionarily diverged hosts, and validate the multihost method of screening for virulence factors relevant to mammalian pathogenesis. Through the use of genetically tractable hosts, the multihost pathogenesis model also provides tools for elucidating host responses and dissecting the fundamental molecular interactions that underlie bacterial pathogenesis.

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