title: A chemical biology approach to interrogate quorum-sensing regulated behaviors at the molecular and cellular level.
abstract: Small molecule probes have been used extensively to explore biologic systems and elucidate cellular signaling pathways. In this study, we use an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering unrecognized processes regulated by AI-2-based quorum-sensing (QS), a mechanism of bacterial intercellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intercellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation.
authors.affiliation: The Skaggs Institute for Chemical Biology, Departments of Chemistry, Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Lowery
authors.forename: Susana
authors.initials: S
authors.lastname: Matamouros
authors.forename: Sherry
authors.initials: S
authors.lastname: Niessen
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Scolnick
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Lively
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
authors.forename: Gunnar F
authors.initials: GF
authors.lastname: Kaufmann
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D006714:Homoserine / Q000031:analogs & derivatives / Q000378:metabolism; D007783:Lactones / Q000378:metabolism; D015336:Molecular Probe Techniques; D010422:Pentanones / Q000494:pharmacology; D040901:Proteomics; D053038:Quorum Sensing / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: C551402:4,5-dihydroxypentane-2,3-dione; D001426:Bacterial Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D010422:Pentanones; D012333:RNA, Messenger; D006714:Homoserine
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