Identification of new quorum sensing autoinducer binding partners in Pseudomonas aeruginosa using photoaffinity probes,Chemical Science

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Identification of new quorum sensing autoinducer binding partners in Pseudomonas aeruginosa using photoaffinity probes
Chemical Science ( IF 7.6 ) Pub Date : 2017-08-29 00:00:00 , DOI: 10.1039/c7sc01270e
Y. R. Baker _{1,

2,

3,

4,

5} , J. T. Hodgkinson _{1,

2,

3,

4,

6} , B. I. Florea _{5,

7,

8,

9} , E. Alza _{1,

2,

3,

4} , W. R. J. D. Galloway _{1,

2,

3,

4} , L. Grimm _{2,

3,

4,

6} , S. M. Geddis _{1,

2,

3,

4} , H. S. Overkleeft _{5,

7,

8,

9} , M. Welch _{2,

3,

4,

6} , D. R. Spring _{1,

2,

3,

4}

Affiliation

Many bacterial species, including the human pathogen Pseudomonas aeruginosa, employ a mechanism of intercellular communication known as quorum sensing (QS), which is mediated by signalling molecules termed autoinducers. The Pseudomonas Quinolone Signal (PQS) and 2-Heptyl-3H-4-Quinolone (HHQ) are autoinducers in P. aeruginosa, and they are considered important factors in the progress of infections by this clinically relevant organism. Herein, we report the development of HHQ and PQS photoaffinity-based probes for chemical proteomic studies. Application of these probes led to the identification of previously unsuspected putative HHQ and PQS binders, thereby providing new insights into QS at a proteomic level and revealing potential new small molecule targets for virulence attenuation strategies. Notably, we found evidence that PQS binds RhlR, the cognate receptor in the Rhl QS sub-system of P. aeruginosa. This is the first indication of interaction between the Rhl and PQS systems at the protein/ligand level, which suggests that RhlR should be considered a highly attractive target for antivirulence strategies.

中文翻译：

使用光亲和探针鉴定铜绿假单胞菌中新的群体感应自动诱导剂结合伴侣

许多细菌物种，包括人类病原体铜绿假单胞菌，都采用一种称为群体感应（QS）的细胞间通讯机制，该机制由称为自动诱导物的信号分子介导。的假单胞菌喹诺酮类信号（PQS）和2-庚基-3- ħ -4-喹诺酮（HHQ）是在自体诱导物铜绿假单胞菌，并且它们被认为是这种临床相关生物感染进程中的重要因素。在这里，我们报告基于HHQ和PQS光亲和力的探针的化学蛋白质组学研究的发展。这些探针的应用导致鉴定了以前未曾怀疑的HHQ和PQS结合剂，从而在蛋白质组学水平上为QS提供了新的见识，并揭示了潜在的新的小分子靶标，用于毒力减弱策略。值得注意的是，我们发现有证据表明PQS与铜绿假单胞菌Rhl QS子系统中的同源受体RhlR结合。这是Rhl和PQS系统在蛋白质/配体水平上相互作用的第一个迹象，这表明RhlR应该被认为是抗毒力策略的极具吸引力的目标。

更新日期：2017-09-14

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