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.
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Acknowledgements
This work was supported by the NIH (R01 GM089999). We thank Dr N Woodford and Dr D Livermore from the Centre for Infections, Health Protection Agency, United Kingdom, for their help with the clinical CF isolates. TM is grateful for the Excellent Young Researchers Overseas Visit Program Fellowship of the Japan Society for the Promotion of Science. RG-C was supported by the SEP/CONACyT grant 152794. TW is the T Michael O’Connor II Endowed Chair and Professor at the Texas A&M University.
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Maeda, T., García-Contreras, R., Pu, M. et al. Quorum quenching quandary: resistance to antivirulence compounds. ISME J 6, 493–501 (2012). https://doi.org/10.1038/ismej.2011.122
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DOI: https://doi.org/10.1038/ismej.2011.122
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