Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/40562
Title: Identification of new quorum sensing autoinducer binding partners in Pseudomonas aeruginosa using photoaffinity probes
Authors: Baker, Y. R.
Hodgkinson, J. T.
Florea, B. I.
Alza, E.
Galloway, W. R. J. D.
Grimm, L.
Geddis, S. M.
Overkleeft, H. S.
Welch, M.
Spring, D. R.
First Published: 29-Aug-2017
Publisher: Royal Society of Chemistry
Citation: Chemical Science, 2017, 8, 7403-7411
Abstract: 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.
DOI Link: 10.1039/C7SC01270E
ISSN: 2041-6520
eISSN: 2041-6539
Links: http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C7SC01270E#!divAbstract
http://hdl.handle.net/2381/40562
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc01270e
Appears in Collections:Published Articles, Dept. of Chemistry

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