The emergence of multidrug-resistant Pseudomonas aeruginosa in healthcare settings poses a tremendous challenge to traditional antibiotic therapy. P. aeruginosa utilizes quorum sensing (QS) to coordinate the production of virulence factors and the formation of drug-resistant biofilms. QS is mediated by signal compounds produced by P. aeruginosa as well as signal molecules produced by other non-pseudomonad bacteria. A potential strategy to prevent bacterial pathogenicity is utilizing enzymes to interfere with QS. Here, we used AidC, a quorum-quenching enzyme from Chryseobacterium sp. strain StRB126 that can effectively hydrolyze N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL) and N-butanoyl-homoserine lactone (C4-HSL), the major signal molecules synthesized by P. aeruginosa. The exogenous addition of AidC to P. aeruginosa wild-type strain PAO1 cultures significantly reduced the total protease and elastase activities and the production of pyocyanin. In addition, the application of AidC resulted in thin and sparse biofilm formation. Later, we used a metagenomic-derived quorum quenching (QQ) enzyme QQ-2 in combination with AidC to attenuate PAO1 virulence when the presence of a non-pseudomonad signal compound AI-2 aggravated it. These findings suggest that using a combined antimicrobial approach may lead to a more efficacious therapeutic intervention against P. aeruginosa PAO1 infection, as its behavior is modulated in the presence of intraspecies and interspecies signal compounds.

中文翻译：

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使用多种群体猝灭酶降低铜绿假单胞菌的毒力

医疗机构中多重耐药铜绿假单胞菌的出现对传统抗生素治疗提出了巨大挑战。铜绿假单胞菌利用群体感应（QS）来协调毒力因子的产生和耐药生物膜的形成。QS 由铜绿假单胞菌产生的信号化合物以及其他非假单胞菌产生的信号分子介导。防止细菌致病性的一个潜在策略是利用酶干扰 QS。在这里，我们使用了 AidC，一种来自 Chryseobacter sp. 的群体淬灭酶。StRB126菌株可以有效水解铜绿假单胞菌合成的主要信号分子N-(3-氧代十二酰基)高丝氨酸内酯(3OC12-HSL)和N-丁酰基-高丝氨酸内酯(C4-HSL)。向铜绿假单胞菌野生型菌株PAO1培养物中外源添加AidC显着降低了总蛋白酶和弹性蛋白酶活性以及绿脓素的产生。此外，AidC 的应用导致了薄而稀疏的生物膜形成。后来，当非假单胞菌信号化合物 AI-2 的存在加剧 PAO1 毒力时，我们使用宏基因组衍生的群体猝灭 (QQ) 酶 QQ-2 与 AidC 组合来减弱 PAO1 毒力。这些发现表明，使用联合抗菌方法可能会对铜绿假单胞菌 PAO1 感染产生更有效的治疗干预，因为其行为在种内和种间信号化合物的存在下受到调节。