Infection control by antibody disruption of bacterial quorum sensing signaling

Chem Biol. 2007 Oct;14(10):1119-27. doi: 10.1016/j.chembiol.2007.08.013.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobutyrates / immunology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Gene Expression Regulation, Bacterial / drug effects*
  • Gene Expression Regulation, Bacterial / physiology
  • Humans
  • Mice
  • Quorum Sensing / drug effects*
  • Quorum Sensing / genetics
  • Quorum Sensing / physiology
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / immunology
  • Virulence Factors / genetics

Substances

  • Aminobutyrates
  • Antibodies, Monoclonal
  • Virulence Factors
  • 2-amino-4-phosphonobutyric acid