Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens
Andromeda-Celeste Gómez, Thérèse Lyons, Uwe Mamat, Daniel Yero, Marc Bravo, Xavier Daura, Osama Elshafee, Sascha Brunke, Cormac G. M. Gahan, Michelle O’Driscoll, Isidre Gibert, Timothy P. O’Sullivan
Abstract
Diseases caused by biofilm-forming pathogens are becoming increasingly prevalent and represent a major threat to human health. This trend has prompted a search for novel inhibitors of microbial biofilms which could, for example, be used to potentiate existing antibiotics. Naturally-occurring, halogenated furanones isolated from marine algae have proven to be effective biofilm inhibitors in several bacterial species. In this work, we report the synthesis of a library of novel furanones and their subsequent evaluation as biofilm inhibitors in several opportunistic human pathogens including S. enterica, S. aureus, E. coli, S. maltophilia, P. aeruginosa and C. albicans. A number of the most potent compounds were subjected to further analysis by confocal laser-scanning microscopy for their effects on P. aeruginosa and C. albicans biofilms individually, in addition to mixed polymicrobial biofilms. Lastly, we investigated the impact of a promising candidate on survival rates in vivo using a Galleria mellonella model.