Infection control by antibody disruption of bacterial quorum sensing signaling.
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.
Park
Junguk
J
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jagasia
Reshma
R
Kaufmann
Gunnar F
GF
Mathison
John C
JC
Ruiz
Diana I
DI
Moss
Jason A
JA
Meijler
Michael M
MM
Ulevitch
Richard J
RJ
Janda
Kim D
KD
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
D000613:Aminobutyrates; D000911:Antibodies, Monoclonal; D037521:Virulence Factors; C012729:2-amino-4-phosphonobutyric acid