Disruption of N -acyl-homoserine lactone-specific signalling and virulence in clinical pathogens by marine sponge bacteria

Abstract

In recent years, the marine environment has been thesubject of increasing attention from biotechnologicaland pharmaceutical industries. A combination ofunique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extremehabitats, underscores the potential of the marine envi-ronment to deliver on functionally novel bioactivities.One such area of ongoing research is the discovery of compounds that interfere with the cell–cell signallingprocess called quorum sensing (QS). Described asthe next generation of antimicrobials, these com-pounds can target virulence and persistence ofclinically relevant pathogens, independent of anygrowth-limiting effects. Marine sponges are a richsource of microbial diversity, with dynamic popula-tions in a symbiotic relationship. In this study, wehave harnessed the QS inhibition (QSI) potential ofmarine sponge microbiota and through culture-baseddiscovery have uncovered small molecule signal mim-ics that neutralize virulence phenotypes in clinicalpathogens. This study describes for thefirst time amarine spongePsychrobactersp. isolate B98C22 thatblocks QS signalling, while also reporting dual QS/QSI activity in thePseudoalteromonassp. J10 andParacoccusJM45. Isolation of novel QSI activities hassignificant potential for future therapeutic develop-ment, of particular relevance in the light of the pend-ing perfect storm of antibiotic resistance meetingantibiotic drug discovery decline.