Maisuria Vimal B, Los Santos Yossef Lopez-de, Tufenkji Nathalie, Déziel Eric
Department of Chemical Engineering, McGill University, 3610 University Street, Montreal, Quebec, Canada.
INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, Québec, Canada.
Sci Rep. 2016 Aug 9;6:30169. doi: 10.1038/srep30169.
Bacteria have evolved multiple strategies for causing infections that include producing virulence factors, undertaking motility, developing biofilms, and invading host cells. N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS) tightly regulates the expression of multiple virulence factors in the opportunistic pathogenic bacterium Pseudomonas aeruginosa. Thus, inhibiting QS could lead to health benefits. In this study, we demonstrate an anti-virulence activity of a cranberry extract rich in proanthocyanidins (cerPAC) against P. aeruginosa in the model host Drosophila melanogaster and show this is mediated by QS interference. cerPAC reduced the production of QS-regulated virulence determinants and protected D. melanogaster from fatal infection by P. aeruginosa PA14. Quantification of AHL production using liquid chromatography-mass spectrometry confirmed that cerPAC effectively reduced the level of AHLs produced by the bacteria. Furthermore, monitoring QS signaling gene expression revealed that AHL synthases LasI/RhlI and QS transcriptional regulators LasR/RhlR genes were inhibited and antagonized, respectively, by cerPAC. Molecular docking studies suggest that cranberry-derived proanthocyanidin binds to QS transcriptional regulators, mainly interacting with their ligand binding sites. These findings provide insights into the underlying mechanisms of action of a cerPAC to restrict the virulence of P. aeruginosa and can have implications in the development of alternative approaches to control infections.
细菌已经进化出多种引起感染的策略，包括产生毒力因子、进行运动、形成生物膜以及侵入宿主细胞。N-酰基高丝氨酸内酯（AHL）介导的群体感应（QS）严格调控机会致病菌铜绿假单胞菌中多种毒力因子的表达。因此，抑制群体感应可能对健康有益。在本研究中，我们证明了富含原花青素的蔓越莓提取物（cerPAC）在模式宿主黑腹果蝇中对铜绿假单胞菌具有抗毒力活性，并表明这是由群体感应干扰介导的。cerPAC减少了群体感应调控的毒力决定因素的产生，并保护黑腹果蝇免受铜绿假单胞菌PA14的致命感染。使用液相色谱-质谱法定量AHL的产生证实，cerPAC有效地降低了细菌产生的AHL水平。此外，监测群体感应信号基因表达发现，cerPAC分别抑制和拮抗了AHL合成酶LasI/RhlI和群体感应转录调节因子LasR/RhlR基因。分子对接研究表明，蔓越莓衍生的原花青素与群体感应转录调节因子结合，主要与其配体结合位点相互作用。这些发现为cerPAC限制铜绿假单胞菌毒力的潜在作用机制提供了见解，并可能对开发控制感染的替代方法具有启示意义。
