Burkholderia cepacia is well known as the causative agent of infections in humans where often shares niche with other pathogens, like Pseudomonas aeruginosa. Clinical isolate Burkholderia sp. BCC4135 was selected due to its strong quorum quenching (QQ) activity. Whole genome sequencing unveiled this isolate as B. cepacia with unique sequence type ST1485 and a myriad of genes belonging to resistome and virulome. Two QQ lactonases YtnP and Y2-aiiA originated from B. cepacia BCC4135 were cloned, expressed, and functionally characterized. They were active against a broad substrate spectrum of the N-acyl-homoserine lactones (AHLs). The YtnP lactonase was inactive, while Y2-aiiA was active against N-tetradecanoyl-dl-homoserine lactone (C14-HSL) which could imply the difference in their biological roles from the aspect of its quorum sensing (QS) autoregulation and interference with the QS systems of bacteria residing within the same niche. Both YtnP and Y2-aiiA were able to attenuate virulence potential of P. aeruginosa MMA83 clinical isolate declining its biofilm formation and virulence factors production. B. cepacia BCC4135 lactonases interfered with the las, rhl, and even pqs QS circuit of P. aeruginosa MMA83 transcription and the effect of combined enzymes was even more prominent. B. cepacia BCC4135 also employs the CepI/R QS system for governing its own virulence traits and possibly self-regulates the QQ/QS network through the different expression and activity of YtnP and/or Y2-aiiA. Our findings pointed out that BCC4135 lactonases could be exploited as an effective antivirulence drugs against P. aeruginosa and gave us a new insight into B. cepacia QQ/QS machinery.

洋葱伯克霍尔德菌是人类感染的病原体，通常与其他病原体（如铜绿假单胞菌）共享利基。临床分离伯克霍尔德菌 选择BCC4135是因为其强大的定额猝灭（QQ）活动。全基因组测序揭示了这种分离株为洋葱伯克霍尔德菌，具有独特的序列类型ST1485和无数属于抵抗基因组和毒理基因组的基因。克隆，表达并在功能上鉴定了源自洋葱伯克霍尔德菌BCC4135的两个QQ内酯酶YtnP和Y2-aiiA 。它们对N-酰基-高丝氨酸内酯（AHL）的较宽的底物谱具有活性。YtnP内酯酶无活性，而Y2-aiiA对N-十四烷酰-dl-高丝氨酸内酯（C14-HSL）从其群体感应（QS）自动调节和干扰位于同一位置的细菌的QS系统方面暗示其生物学作用的差异。YtnP和Y2-aiiA都能够减弱铜绿假单胞菌MMA83临床分离株的毒力潜力，从而降低其生物膜形成和毒力因子的产生。洋葱伯克霍尔德菌BCC4135内切酶干扰铜绿假单胞菌MMA83转录的las，rhl甚至pqs QS回路，并且组合酶的作用更加突出。洋葱芥BCC4135还使用CepI / R QS系统管理其自身的毒力特征，并可能通过YtnP和/或Y2-aiiA的不同表达和活性来自我调节QQ / QS网络。我们的研究结果表明，BCC4135内切酶可以作为一种有效的抗铜绿假单胞菌的抗毒药物，为我们提供了对洋葱败血假单胞菌QQ / QS机械的新见解。