Quorum quenching quandary: Resistance to antivirulence compounds

Toshinari Maeda, Rodolfo García-Contreras, Mingming Pu, Lili Sheng, Luis Rene Garcia, Maria Tomás, Thomas K. Wood

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Quorum sensing (QS) is the regulation of gene expression in response to the concentration of small signal molecules, and its inactivation has been suggested to have great potential to attenuate microbial virulence. It is assumed that unlike antimicrobials, inhibition of QS should cause less Darwinian selection pressure for bacterial resistance. Using the opportunistic pathogen Pseudomonas aeruginosa, we demonstrate here that bacterial resistance arises rapidly to the best-characterized compound that inhibits QS (brominated furanone C-30) due to mutations that increase the efflux of C-30. Critically, the C-30-resistant mutant mexR was more pathogenic to Caenorhabditis elegans in the presence of C-30, and the same mutation arises in bacteria responsible for chronic cystic fibrosis infections. Therefore, bacteria may evolve resistance to many new pharmaceuticals thought impervious to resistance.

Original languageEnglish (US)
Pages (from-to)493-501
Number of pages9
JournalISME Journal
Volume6
Issue number3
DOIs
StatePublished - Mar 2012

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics

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