Department of Microbiology, School of Medicine, Marmara University, Haydarpasa, Istanbul, Turkey.
Clin Microbiol Infect. 2010 Dec;16(12):1770-5. doi: 10.1111/j.1469-0691.2010.03177.x.
Pseudomonas aeruginosa is an opportunistic pathogen causing severe respiratory infections. The pathogenesis of these infections is multifactorial and the production of many virulence factors is regulated by quorum sensing (QS), a cell-to-cell communication mechanism. The two well defined QS systems in P. aeruginosa, the las and rhl systems, rely on N-acyl homoserine lactone signal molecules, also termed autoinducers. We assessed the activity of QS-dependent virulence factors (including elastase, alkaline protease, pyocyanin and biofilm production) in respiratory isolates of P. aeruginosa and their relationship with antimicrobial susceptibility. We identified sixteen isolates displaying impaired phenotypic activity; among them, eleven isolates were also defective in autoinducer production, and therefore considered QS-deficient. Six of the QS-deficient isolates failed to amplify one or more of the four QS regulatory genes (lasI, lasR, rhlI, rhlR) with PCR: one isolate was negative for rhlR, two isolates were negative for rhlI and rhlR and three isolates were negative for all four genes. The isolates that were negative for virulence factor production were generally less susceptible to the antimicrobials and statistically significant correlations were observed between the lack of elastase production and resistance to piperacillin and ceftazidime; between failure in alkaline protease production and resistance to tobramycin, piperacillin, piperacillin-tazobactam, cefepime, imipenem and ciprofloxacin; and between failure in pyocyanin production and resistance to amikacin, tobramycin, ceftazidime, ciprofloxacin and ofloxacin. The results obtained indicate that, despite the pivotal role of QS in the pathogenesis of P. aeruginosa respiratory infections, QS-deficient strains are still capable of causing infections and tend to be less susceptible to antimicrobials.
铜绿假单胞菌是一种机会性病原体，可导致严重的呼吸道感染。这些感染的发病机制是多因素的，许多毒力因子的产生受群体感应（QS）调节，这是一种细胞间通讯机制。铜绿假单胞菌中有两个定义明确的 QS 系统，即 las 和 rhl 系统，它们依赖于 N-酰基高丝氨酸内酯信号分子，也称为自诱导物。我们评估了铜绿假单胞菌呼吸道分离株中依赖 QS 的毒力因子（包括弹性蛋白酶、碱性蛋白酶、绿脓菌素和生物膜形成）的活性及其与抗菌药物敏感性的关系。我们确定了 16 株表现出表型活性受损的分离株；其中，11 株分离株也缺乏自诱导物的产生，因此被认为是 QS 缺陷型。6 株 QS 缺陷型分离株未能通过 PCR 扩增 4 个 QS 调节基因（lasI、lasR、rhlI、rhlR）中的一个或多个：1 株分离株 rhlR 为阴性，2 株分离株 rhlI 和 rhlR 为阴性，3 株分离株均为阴性所有四个基因。缺乏毒力因子产生的分离株通常对抗菌药物的敏感性较低，并且弹性蛋白酶产生的缺乏与哌拉西林和头孢他啶的耐药性之间、碱性蛋白酶产生的缺乏与妥布霉素、哌拉西林、哌拉西林-他唑巴坦、头孢吡肟、亚胺培南和环丙沙星的耐药性之间、以及绿脓菌素产生的缺乏与阿米卡星、妥布霉素、头孢他啶、环丙沙星和氧氟沙星的耐药性之间均存在统计学显著相关性。结果表明，尽管 QS 在铜绿假单胞菌呼吸道感染的发病机制中起着关键作用，但 QS 缺陷型菌株仍能引起感染，并且往往对抗菌药物的敏感性较低。
