caa a22 4500 60550010X CHVBK 20210128100554.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00253-015-6436-1 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6436-1 Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens [Elektronische Daten] [José Gutiérrez-Barranquero, F. Reen, Ronan McCarthy, Fergal O'Gara] The rapid unchecked rise in antibiotic resistance over the last few decades has led to an increased focus on the need for alternative therapeutic strategies for the treatment and clinical management of microbial infections. In particular, small molecules that can suppress microbial virulence systems independent of any impact on growth are receiving increased attention. Quorum sensing (QS) is a cell-to-cell signalling communication system that controls the virulence behaviour of a broad spectrum of bacterial pathogens. QS systems have been proposed as an effective target, particularly as they control biofilm formation in pathogens, a key driver of antibiotic ineffectiveness. In this study, we identified coumarin, a natural plant phenolic compound, as a novel QS inhibitor, with potent anti-virulence activity in a broad spectrum of pathogens. Using a range of biosensor systems, coumarin was active against short, medium and long chain N-acyl-homoserine lactones, independent of any effect on growth. To determine if this suppression was linked to anti-virulence activity, key virulence systems were studied in the nosocomial pathogen Pseudomonas aeruginosa. Consistent with suppression of QS, coumarin inhibited biofilm, the production of phenazines and swarming motility in this organism potentially linked to reduced expression of the rhlI and pqsA quorum sensing genes. Furthermore, coumarin significantly inhibited biofilm formation and protease activity in other bacterial pathogens and inhibited bioluminescence in Aliivibrio fischeri. In light of these findings, coumarin would appear to have potential as a novel quorum sensing inhibitor with a broad spectrum of action. Springer-Verlag Berlin Heidelberg, 2015 Coumarin nationallicence Natural compound nationallicence Quorum sensing inhibition nationallicence Anti-biofilm nationallicence Bacterial pathogens nationallicence Gutiérrez-Barranquero José BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut Reen F. BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut McCarthy Ronan BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut O'Gara Fergal BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/7(2015-04-01), 3303-3316 0175-7598 99:7<3303 2015 99 253 https://doi.org/10.1007/s00253-015-6436-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6436-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gutiérrez-Barranquero José BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut NATIONALLICENCE 700 1- Reen F. BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut NATIONALLICENCE 700 1- McCarthy Ronan BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut NATIONALLICENCE 700 1- O'Gara Fergal BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/7(2015-04-01), 3303-3316 0175-7598 99:7<3303 2015 99 253