Promising MRSA VAccine Targets Quorum Sensing

Filed in archive Drugs, Vaccines and Therapeutics , Genomics, Proteomics and Bioinformatics on November 9, 2007

A new type of vaccine against resistant bacterial strains, particularly methicillin resistant Staphylococcus aureus (MRSA), is being developed.

Rather than killing bacteria, the new vaccine works by blocking the bacteria's quorum sensing, a communication system that allows them to shift from being harmless to virulent. The shift to virulence is dependent on small molecules emitted by bacteria known as autoinducers, sequestration of which could therefore block quorum sensing and the establishment of infections.

The Scripps Research team focused on Gram-positive bacteria, whose quorum sensing is controlled by four basic types of autoinducers tied to a circuit known as the accessory gene regulator. Based on the known structure of one of these autoinducers, the team designed a molecule known as a hapten that, when conjugated with specific proteins using well-established procedures, induces the production of antibodies by the immune system.

Next, the team isolated and studied the antibodies produced in mice injected with the hapten, called AP4. Subsequent experiments revealed that one of these antibodies in particular, when administered to mice infected with Staphylococcus aureus, was highly effective at binding with and sequestering the targeted autoinducer, and to a lesser extent with a second autoinducer. This activity proved to effectively block quorum sensing and infection in the mice.

This antibody, called AP4-24H11, may be given as a passive vaccine to block infections, while the AP4 hapten could also be applied as an active vaccine that would induce production of antibodies to block quorum sensing. This study appears in the journal Chemistry and Biology.

Source: Science Daily
Photo Credit: CDC/Jim Biddle