dc.contributor.author	An, Shi-qi
dc.contributor.author	Murtagh, Julie
dc.contributor.author	Twomey, Kate B.
dc.contributor.author	Gupta, Manoj K.
dc.contributor.author	O'Sullivan, Timothy P.
dc.contributor.author	Ingram, Rebecca
dc.contributor.author	Valvano, Miguel A.
dc.contributor.author	Tang, Ji-liang
dc.contributor.funder	Wellcome Trust	en
dc.contributor.funder	Biotechnology and Biological Sciences Research Council	en
dc.date.accessioned	2019-11-20T05:49:29Z
dc.date.available	2019-11-20T05:49:29Z
dc.date.issued	2019-05-27
dc.description.abstract	Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.	en
dc.description.sponsorship	Wellcome (100204/A/12/Z); Ba Gui Scholar Program (2014A002)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.articleid	2334	en
dc.identifier.citation	An, S.Q., Murtagh, J., Twomey, K.B., Gupta, M.K., O’Sullivan, T.P., Ingram, R., Valvano, M.A. and Tang, J.L., 2019. Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues. Nature communications, 10(1), (2334). DOI:10.1038/s41467-019-10271-4	en
dc.identifier.doi	10.1038/s41467-019-10271-4	en
dc.identifier.eissn	2041-1723
dc.identifier.endpage	11	en
dc.identifier.journaltitle	Nature Communications	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/9143
dc.identifier.volume	10	en
dc.language.iso	en	en
dc.publisher	Nature Publishing Group	en
dc.relation.project	info:eu-repo/grantAgreement/RCUK/BBSRC/BB/R012415/1/GB/National Biofilms Innovation Centre/	en
dc.relation.uri	https://www.nature.com/articles/s41467-019-10271-4
dc.rights	© The Author(s) 2019	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	en
dc.subject	Pseudomonas aeruginosa	en
dc.subject	Antibiotic sensitivity	en
dc.subject	Biofilm formation	en
dc.subject	Interspecies signal analogues	en
dc.subject	Pathogen	en
dc.title	Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues	en
dc.type	Article (peer-reviewed)	en

Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues

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