Quorum quenching quandary: resistance to antivirulence compounds

被引:215
作者
Maeda, Toshinari [1 ,2 ]
Garcia-Contreras, Rodolfo [3 ,4 ]
Pu, Mingming [1 ]
Sheng, Lili [1 ,5 ]
Garcia, Luis Rene [6 ]
Tomas, Maria [7 ]
Wood, Thomas K. [1 ,6 ]
机构
[1] Texas A&M Univ, Dept Chem Engn, College Stn, TX 77843 USA
[2] Kyushu Inst Technol, Dept Biol Funct & Engn, Kitakyushu, Fukuoka 804, Japan
[3] Natl Inst Cardiol, Dept Biochem, Mexico City, DF, Mexico
[4] Vrije Univ Amsterdam, Dept Mol Cell Physiol, Amsterdam, Netherlands
[5] E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China
[6] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA
[7] CH Univ A Coruna INIBIC, Unidad Invest Microbiol, La Coruna, Spain
基金
日本学术振兴会;
关键词
drug resistance; efflux pump; Pseudomonas aeruginosa; quorum sensing; quorum quenching; PSEUDOMONAS-AERUGINOSA; BIOFILM FORMATION; ESCHERICHIA-COLI; GENE-EXPRESSION; SWARMING MOTILITY; CYSTIC-FIBROSIS; VIRULENCE; IDENTIFICATION; INHIBITION; TRANSPORT;
D O I
10.1038/ismej.2011.122
中图分类号
Q14 [生态学(生物生态学)];
学科分类号
071012 ; 0713 ;
摘要
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. The ISME Journal (2012) 6, 493-501; doi: 10.1038/ismej.2011.122; published online 15 September 2011
引用
收藏
页码:493 / 501
页数:9
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