New peptide mimics inhibit pathogenic bacteria involved in toxic shock syndrome
May 13, 2013 § Leave a comment
The pathogenic bacterium Staphylococcus aureus believes in the power of numbers to bring on infections, such as toxic shock syndrome. In a paper just out in the Journal of the American Chemical Society, researchers describe potent inhibitors that stop the bacterium from forming its armies.
Bacteria use small molecules or peptides as signals to communicate with each other. This phenomenon is known as quorum sensing and it plays a critical role in a bacterium’s virulence. “If we can block quorum sensing, we can effectively tune the infectivity of this major pathogen,” explains Helen Blackwell.
Blackwell’s laboratory at the University of Wisconsin-Madison is focused on understanding how these small molecules and peptides function and is developing non-native mimetics of these compounds. These mimetics can be used as chemical probes to study the fundamental mechanisms of quorum sensing.
For this work, Blackwell and her group studied the structure and function of a S. aureus peptide called AIP-III. This peptide is critical for the bacterium’s quorum sensing system and plays a central role in initiating toxic shock syndrome in humans. The investigators made a series of AIP-III analogs that mimicked the native peptide’s structure. Then they tweaked small parts in these analogs to see if that part was important for the peptide’s function: They identified a series of parts they could tweak to make the peptide unable to activate quorum sensing but instead strongly inhibit it.
These S. aureus quorum-sensing inhibitors are “the most active peptide-based quorum-sensing inhibitors to be reported in S. aureus,” she explains. “They can block virulence pathways in wild-type S. aureus at very low concentrations. Such lead compounds are a great place to start for the development of new agents for possible anti-infective therapies.”
The investigators are currently working on improving the inhibitor’s chemical stability in biological media so that they can remain active for longer and be more potent.