Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Department of Veterinary Pathobiology, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2017 Aug 29;7(1):9857. doi: 10.1038/s41598-017-09886-8.
For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline.
在过去的十年中，化学控制细菌毒力受到了相当多的关注。大蒜中的一种富含硫的分子——ajoene，已被证明可以降低机会性病原体铜绿假单胞菌中关键群体感应调节毒力因子的表达。在这里，我们表明 ajoene 对群体感应的抑制作用是通过抑制铜绿假单胞菌和另一种重要的人类病原体金黄色葡萄球菌中小的调节 RNA（sRNA）实现的，金黄色葡萄球菌利用群体感应来控制毒力基因的表达。使用各种报告构建体，我们发现 ajoene 降低了铜绿假单胞菌中 RsmY 和 RsmZ 以及控制关键毒力因子表达的小双功能调节 RNA RNAIII 的表达。我们通过 RNA 测序证实了 RNAIII 的调节，并且发现在存在 ajoene 的情况下，金黄色葡萄球菌中许多编码毒力因子（如溶血素和蛋白酶）的 QS 调节基因的表达降低。重要的是，我们的发现表明，跨细菌物种的 sRNA 可能有资格成为抗毒力治疗的靶点，并且 ajoene 可能是一种寻找超越革兰氏阴性阳性边界的广谱化合物的先导结构。
