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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.

SUBMITTER: Park J

PROVIDER: S-EPMC2088803 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Infection control by antibody disruption of bacterial quorum sensing signaling.

Park Junguk J 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

Chemistry & biology 20071001 10

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 effi ...[more]

PMID: 17961824

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Project description:Bacterial-bioluminescence regulation is often associated with quorum sensing. Indeed, many studies have been made on this subject and indicate that the expression of the light-emission-involved genes is density dependent. However, most of these studies have concerned two model species, Aliivibrio fischeri and Vibrio campbellii. Very few works have been done on bioluminescence regulation for the other bacterial genera. Yet, according to the large variety of habitats of luminous marine bacteria, it would not be surprising to find different light-regulation systems. In this study, we used Photobacterium phosphoreum ANT-2200, a piezophilic bioluminescent strain isolated from Mediterranean deep-sea waters (2200-m depth). To answer the question of whether or not the bioluminescence of P. phosphoreum ANT-2200 is under quorum-sensing control, we focused on the correlation between growth and light emission through physiological, genomic and, transcriptomic approaches. Unlike A. fischeri and V. campbellii, the light of P. phosphoreum ANT-2200 immediately increases from its initial level. Interestingly, the emitted light increases at much higher rate at the low cell density than it does for higher cell-density values. The expression level of the light-emission-involved genes stays constant all along the exponential growth phase. We also showed that, even when more light is produced, when the strain is cultivated at high hydrostatic pressure, no change in the transcription level of these genes can be detected. Through different experiments and approaches, our results clearly indicate that, under the tested conditions, the genes, directly involved in the bioluminescence in P. phosphoreum ANT-2200, are not controlled at a transcriptomic level. Quite obviously, these results demonstrate that the light emission of the strain is not density dependent, which means not under quorum-sensing control. Through this study, we point out that bacterial-bioluminescence regulation should not, from now on, be always linked with the quorum-sensing control.

Dataset Information

Infection control by antibody disruption of bacterial quorum sensing signaling.

Publications

Infection control by antibody disruption of bacterial quorum sensing signaling.

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