title: Infection control by antibody disruption of bacterial quorum sensing signaling.
abstract: Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24H11, was elicited against a rationally designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Junguk
authors.initials: J
authors.lastname: Park
authors.forename: Reshma
authors.initials: R
authors.lastname: Jagasia
authors.forename: Gunnar F
authors.initials: GF
authors.lastname: Kaufmann
authors.forename: John C
authors.initials: JC
authors.lastname: Mathison
authors.forename: Diana I
authors.initials: DI
authors.lastname: Ruiz
authors.forename: Jason A
authors.initials: JA
authors.lastname: Moss
authors.forename: Michael M
authors.initials: MM
authors.lastname: Meijler
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Ulevitch
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000613:Aminobutyrates / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D053038:Quorum Sensing / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000613:Aminobutyrates; D000911:Antibodies, Monoclonal; D037521:Virulence Factors; C012729:2-amino-4-phosphonobutyric acid