title: Antibody interference with N-acyl homoserine lactone-mediated bacterial quorum sensing.
abstract: Many bacterial pathogens coordinate their virulence factor expression in a cell density-dependent manner. This population-dependent coordination of gene expression in bacteria has been termed "quorum sensing" (QS). N-Acyl homoserine lactones (AHLs) are used by over 70 Gram-negative bacterial species as autoinducers. Inhibition of QS signaling might represent a new target for antimicrobial therapy. Here we report the hapten design, synthesis, generation of monoclonal antibodies (mAbs) against AHLs, and the evaluation of these mAbs for their ability to blunt QS signaling and inhibit virulence factor expression in P. aeruginosa. The mAbs can be envisioned as a tool for future investigations into AHL-based QS, which may aid in gaining new insights into the pathogenesis of P. aeruginosa and may ultimately lead to the development of new strategies to combat bacterial diseases.
authors.affiliation: The Skaggs Institute for Chemical Biology and Departments of Chemistry and Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Gunnar F
authors.initials: GF
authors.lastname: Kaufmann
authors.forename: Rafaella
authors.initials: R
authors.lastname: Sartorio
authors.forename: Sang-Hyeup
authors.initials: SH
authors.lastname: Lee
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Mee
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Altobell
authors.forename: David P
authors.initials: DP
authors.lastname: Kujawa
authors.forename: Emily
authors.initials: E
authors.lastname: Jeffries
authors.forename: Bruce
authors.initials: B
authors.lastname: Clapham
authors.forename: Michael M
authors.initials: MM
authors.lastname: Meijler
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000502:physiology; D006241:Haptens / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D006241:Haptens; C088386:homoserine lactone; D015107:4-Butyrolactone