Author/Authors :
Junguk Park، نويسنده , , Reshma Jagasia، نويسنده , , Gunnar F. Kaufmann، نويسنده , , John C. Mathison، نويسنده , , Diana I. Ruiz، نويسنده , , Jason A. Moss، نويسنده , , Michael M. Meijler، نويسنده , , Richard J. Ulevitch، نويسنده , , Kim D. Janda and Ian A. Wilson، نويسنده ,
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.