Antibiotic-resistant hospital pathogens are not to be underestimated as a health risk. A research team has now introduced a new approach for treating multiple-drug resistant Staphylococcus in the journal Angewandte Chemie. It is based on a synthetic peptide that reduces the virulence of the bacteria by blocking their communication by “quorum sensing.” Controlled release of the drug from degradable microparticles very strongly inhibited skin wound infections in an animal model.
As their point of attack, the interdisciplinary team working with Helen E. Blackwell at the University of Wisconsin chose a chemical communication system used by bacteria to communicate with each other, called quorum sensing (QS). Many bacteria use QS to regulate the production of virulence factors, or toxins, involved in infections. Among other things, virulence factors give pathogens the ability to attach to host cells and enter them.
S .aureus and related bacteria have a QS circuit based on the “accessory gene regulator” (agr) system. The QS signal molecule is called the “autoinducing peptide” (AIP). The research team developed a synthetic peptide similar to AIP that blocks the agr system with unusual effectiveness, also blocking QS. Omitting an end part of the peptide chain significantly slowed the degradation of the inhibitor peptide in tissue. Encapsulation of the inhibitor in biodegradable polymer particles allowed for delayed release, prolonging the period of activity—making high effectiveness at a low dose possible. In a mouse model for skin abscess, infections with S. aureus could be almost completely blocked by a local injection of the encapsulated peptide.
This new inhibitor peptide could provide an approach to therapeutic strategies for fighting bacterial infections and may provide new insights into the role of agr and QS in chronic infections. In addition, it could be the foundation for the development of coatings that block bacterial infections for applications like implants.