ENVIRONMENTAL BIOTECHNOLOGY Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens José A. Gutiérrez-Barranquero & F. Jerry Reen & Ronan R. McCarthy & Fergal O’Gara Received: 10 November 2014 /Revised: 6 January 2015 /Accepted: 25 January 2015 # Springer-Verlag Berlin Heidelberg 2015 Abstract 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 con- trol 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 lac- tones, independent of any effect on growth. To determine if this suppression was linked to anti-virulence activity, key vir- ulence 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. Keywords Coumarin . Natural compound . Quorum sensing inhibition . Anti-biofilm . Bacterial pathogens Introduction The emergence of multidrug-resistant bacteria over the last few decades has become a global health issue for medical professionals and public health systems throughout the world (Tanwar et al. 2014). Once the cornerstone of medical inter- vention to treat microbial infections, the indiscriminate use of antibiotics has contributed to the evolution of broad spectrum resistance mechanisms (Fernández and Hancock 2012). In most cases, the selective pressure underpinning the emergence of resistant strains has arisen due to the mode of action of antibiotics, i.e. inhibiting bacterial growth. In the last decade, there has been a sharp decline in the development of new classes of antibiotics, with the result that resistance is continu- ing to increase unchecked. Furthermore, the realisation that microbial communities exist predominantly as multicellular antibiotic-refractive aggregates called biofilms in situ has fur- ther emphasised the challenge facing antibiotic therapies in the clinic. Therefore, there is an urgent need for the develop- ment of alternative therapies that (1) can target these multidrug-resistant isolates in the biofilm state and (2) are less likely to select for resistant strains (Cegelski et al. 2008; Coo- per and Shlaes 2011; LaSarre and Federle 2013). Electronic supplementary material The online version of this article (doi:10.1007/s00253-015-6436-1) contains supplementary material, which is available to authorized users. J. A. Gutiérrez-Barranquero : F. J. Reen : R. R. McCarthy : F. O’Gara (*) BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland e-mail: f.ogara@ucc.ie F. O’Gara School of Biomedical Sciences, Curtin University, Perth WA 6845, Australia Appl Microbiol Biotechnol DOI 10.1007/s00253-015-6436-1