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Abstract：
Pseudomonas aeruginosa is a widespread γ-proteobacterium and an important opportunistic pathogen. The genetically diverse P. aeruginosa phylogroup 3 strains are characterized by producing the pore-forming ExlA toxin and by their lack of a type III secretion system. However, like all strains of this species, they produce several virulence-associated traits, such as elastase, rhamnolipids and pyocyanin, which are regulated by quorum sensing (QS). The P. aeruginosa QS response comprises three systems (Las, Rhl and Pqs, respectively) that hierarchically regulate these virulence factors. The Pqs QS system is composed of the PqsR transcriptional factor, which, coupled with the alkyl-quinolones HHQ or PQS, activates the transcription of the pqsABCDE operon. The products of the first four genes of this operon produce HHQ, which is then converted to PQS by PqsH, while PqsE forms a complex with RhlR and stabilizes it. In this study we report that mutations affecting the Pqs system are particularly common in phylogroup 3 strains. To better understand QS in phylogroup 3 strains we studied strain MAZ105 isolated from tomato rhizosphere and showed that it contains mutations in the central QS transcriptional regulator, LasR, and in the gene encoding the PqsA enzyme involved in the synthesis of PQS. However, it can still produce QS-regulated virulence factors and is virulent in Galleria mellonella and mildly pathogenic in the mouse abscess/necrosis model; our results show that this may be due to the expression of pqsE from a different PqsR-independent promoter than the pqsA promoter. Our results indicate that using anti-virulence therapy based on targeting the PQS system will not be effective against infections by P. aeruginosa phylogroup 3 strains.
摘要：
铜绿假单胞菌是一种广泛存在的γ-蛋白细菌,是一种重要的机会致病菌。遗传多样性的铜绿假单胞菌系统系3菌株的特征在于产生成孔的ExlA毒素并且缺乏III型分泌系统。然而,像这个物种的所有菌株一样，它们产生几个与毒力相关的性状，如弹性蛋白酶，鼠李糖脂和青苷，由群体感应(QS)调节。铜绿假单胞菌QS反应包括三个系统(Las，Rhl和Pqs，分别)分级调节这些毒力因子。PqsQS系统由PqsR转录因子组成，which,与烷基喹诺酮HHQ或PQS偶联，激活pqsABCDE操纵子的转录。该操纵子的前四个基因的产物产生HHQ，然后通过PqsH转换为PQS，而PqsE与RhlR形成复合物并使其稳定。在这项研究中，我们报道了影响Pqs系统的突变在系统组3菌株中特别常见。为了更好地了解系统组3菌株中的QS，我们研究了从番茄根际分离的菌株MAZ105，并表明它在中心QS转录调节因子中含有突变，LasR,以及编码参与PQS合成的PqsA酶的基因。然而,它仍然可以产生QS调节的毒力因子，并且在Galleriamellonella中具有毒力，并且在小鼠脓肿/坏死模型中具有轻度致病性；我们的结果表明，这可能是由于pqsE从与pqsA启动子不同的PqsR非依赖性启动子表达。我们的结果表明，使用基于靶向PQS系统的抗毒力治疗对铜绿假单胞菌系统群3菌株的感染无效。
