Welsh Michael A, Blackwell Helen E
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.
Cell Chem Biol. 2016 Mar 17;23(3):361-9. doi: 10.1016/j.chembiol.2016.01.006. Epub 2016 Feb 18.
Nutritional cues differentially influence the activities of the three quorum sensing (QS) circuits-Las, Rhl, and Pqs-in the pathogen Pseudomonas aeruginosa. A full understanding of how these systems work together to tune virulence factor production to the environment is lacking. Here, we used chemical probes to evaluate the contribution of each QS circuit to virulence in wild-type P. aeruginosa under defined environmental conditions. Our results indicate that Rhl and Pqs drive virulence factor production in phosphate- and iron-limiting environments, while Las has a minor influence. Consequently, simultaneous inhibition of Rhl and Pqs can attenuate virulence in environments where Las inhibition fails. The activity trends generated in this study can be extrapolated to predict QS inhibitor activity in infection-relevant environments, such as cystic fibrosis sputum. These results indicate that environmental signals can drastically alter the efficacy of small-molecule QS inhibitors in P. aeruginosa and possibly other pathogens.
营养信号对病原体铜绿假单胞菌中三种群体感应（QS）系统——Las、Rhl和Pqs的活性有不同影响。目前尚缺乏对这些系统如何协同工作以根据环境调节毒力因子产生的全面了解。在此，我们使用化学探针评估了在特定环境条件下，每个QS系统对野生型铜绿假单胞菌毒力的贡献。我们的结果表明，Rhl和Pqs在磷酸盐和铁限制的环境中驱动毒力因子的产生，而Las的影响较小。因此，在Las抑制失效的环境中，同时抑制Rhl和Pqs可减弱毒力。本研究中产生的活性趋势可外推以预测感染相关环境（如囊性纤维化痰液）中的QS抑制剂活性。这些结果表明，环境信号可极大地改变小分子QS抑制剂对铜绿假单胞菌以及可能对其他病原体的功效。
