Inhibition of quorum sensing in Serratia marcescens AS-1 by synthetic analogs of N-acylhomoserine lactone.
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.
Department of Applied Chemistry, Utsunomiya University, 7-1-2 Yoto, Utsunomiya 321-8585, Japan. morohosi@cc.utsunomiya-u.ac.jp
Tomohiro
T
Morohoshi
Toshitaka
T
Shiono
Kiyomi
K
Takidouchi
Masashi
M
Kato
Norihiro
N
Kato
Junichi
J
Kato
Tsukasa
T
Ikeda
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000032:analysis; D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D011353:Prodigiosin / Q000378:metabolism; D053038:Quorum Sensing / Q000187:drug effects*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D012706:Serratia marcescens / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D015398:Signal Transduction
D001426:Bacterial Proteins; D003517:Cyclopentanes; D004269:DNA, Bacterial; D005663:Furans; D012336:RNA, Ribosomal, 16S; C088386:homoserine lactone; D011353:Prodigiosin; D015107:4-Butyrolactone