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

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journal contribution
posted on 21.11.2017, 10:04 by Y. R. Baker, J. T. Hodgkinson, B. I. Florea, E. Alza, W. R. J. D. Galloway, L. Grimm, S. M. Geddis, H. S. Overkleeft, M. Welch, D. R. Spring
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.

Funding

The CMST COST (European Cooperation in Science and Technology) action CM1004 was involved in funding and supporting the collaborative nature of the research. Work in the D. R. S. lab is also supported by the BBSRC, EPSRC, ERC (FP7/2007-2013; 279337/DOS) and the Wellcome Trust. Work in the M. W. lab is supported by the BBSRC, the European Union and the Rosetrees Trust. Y. R. B. was an EPSRC-funded PhD student. J. T. H. was supported by Trinity College, Cambridge, UK.

History

Citation

Chemical Science, 2017, 8, 7403-7411

Author affiliation

/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of Chemistry

Version

VoR (Version of Record)

Published in

Chemical Science

Publisher

Royal Society of Chemistry

issn

2041-6520

eissn

2041-6539

Acceptance date

26/08/2017

Copyright date

2017

Available date

21/11/2017

Publisher version

http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C7SC01270E#!divAbstract

Notes

Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc01270e

Language

en

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