title: Quorum quenching quandary: resistance to antivirulence compounds.
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.
authors.affiliation: Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Maeda
authors.forename: Rodolfo
authors.initials: R
authors.lastname: García-Contreras
authors.forename: Mingming
authors.initials: M
authors.lastname: Pu
authors.forename: Lili
authors.initials: L
authors.lastname: Sheng
authors.forename: Luis Rene
authors.initials: LR
authors.lastname: Garcia
authors.forename: Maria
authors.initials: M
authors.lastname: Tomás
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D017173:Caenorhabditis elegans; D024881:Drug Resistance, Bacterial; D019143:Evolution, Molecular; D005663:Furans / Q000378:metabolism / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D053038:Quorum Sensing / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D059467:Transcriptome; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D005663:Furans; C423620:MexR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; C494198:furanone C-30