Inhibition of Quorum Sensing in Serratia marcescens AS-1 by Synthetic Analogs of N -Acylhomoserine Lactone

Abstract

ABSTRACT Quorum sensing is a regulatory system for controlling gene expression in response to increasing cell density. N -Acylhomoserine lactone (AHL) is produced by gram-negative bacteria, which use it as a quorum-sensing signal molecule. Serratia marcescens is a gram-negative opportunistic pathogen which is responsible for an increasing number of serious nosocomial infections. S. marcescens AS-1 produces N -hexanoyl homoserine lactone (C 6 -HSL) and N -(3-oxohexanoyl) homoserine lactone and regulates prodigiosin production, swarming motility, and biofilm formation by AHL-mediated quorum sensing. We synthesized a series of N -acyl cyclopentylamides with acyl chain lengths ranging from 4 to 12 and estimated their inhibitory effects on prodigiosin production in AS-1. One of these molecules, N -nonanoyl-cyclopentylamide (C 9 -CPA), had a strong inhibitory effect on prodigiosin production. C 9 -CPA also inhibited the swarming motility and biofilm formation of AS-1. A competition assay revealed that C 9 -CPA was able to inhibit quorum sensing at four times the concentration of exogenous C 6 -HSL and was more effective than the previously reported halogenated furanone. Our results demonstrated that C 9 -CPA was an effective quorum-sensing inhibitor for S. marcescens AS-1.