A broad range quorum sensing inhibitor working through sRNA inhibition.
A broad range quorum sensing inhibitor working through sRNA inhibition.
复制标题
通过SRNA抑制作用的范围群体传感抑制剂。
DOI：
10.1038/s41598-017-09886-8
复制
发表时间：
2017-08-29
影响因子：
4.6
通讯作者：
Givskov M
中科院分区：
文献类型：
--
作者：
Jakobsen TH;Warming AN;Vejborg RM;Moscoso JA;Stegger M;Lorenzen F;Rybtke M;Andersen JB;Petersen R;Andersen PS;Nielsen TE;Tolker-Nielsen T;Filloux A;Ingmer H;Givskov M
在过去的十年中，细菌毒力的化学控制受到了相当大的关注。阿焦烯，一种来自大蒜的富含硫的分子，已被证明可以减少机会致病菌铜绿假单胞菌中关键的群体感应调节毒力因子的表达。在这里，我们表明，抑制效应的ajoene对群体感应发生的抑制小调控RNA（sRNA）在铜绿假单胞菌以及金黄色葡萄球菌，另一个重要的人类病原体，采用群体感应控制毒力基因的表达。使用各种报告基因构建体，我们发现阿焦烯降低了铜绿假单胞菌中sRNA RsmY和RsmZ的表达，以及S.金黄色葡萄球菌，其控制关键毒力因子的表达。我们通过RNA测序证实了RNAIII的调节作用，并发现在S.金黄色的重要的是，我们的研究结果表明，跨细菌物种的sRNAs可能有资格作为抗病毒治疗的靶标，并且阿焦烯可能是寻找超越革兰氏阴性-阳性边界的广谱化合物的先导结构。
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.
登录
查看更多内容
影响因子：
2.8
作者：
Burrowes, E;Baysse, C;O'Gara, F
通讯作者：
O'Gara, F
影响因子：
10.5
作者：
Boisset, Sandrine;Geissmann, Thomas;Romby, Pascale
通讯作者：
Romby, Pascale
影响因子：
28.3
作者：
Broder, Ursula N.;Jaeger, Tina;Jenal, Urs
通讯作者：
Jenal, Urs
影响因子：
4.9
作者：
Chiang, Wen-Chi;Nilsson, Martin;Tolker-Nielsen, Tim
通讯作者：
Tolker-Nielsen, Tim
影响因子：
3.1
作者：
DeLeon, Stephanie;Clinton, Allie;Rumbaugh, Kendra P.
通讯作者：
Rumbaugh, Kendra P.