Toxin and antitoxin (TA) systems are commonly found in prokaryotes. These systems function to allow the organisms to rapidly adjust rates of protein and DNA synthesis in order to respond to external stimuli and/or stress. Among these TA systems is the MazEF system, which includes the toxin MazF and the antitoxin MazE. The MazF toxin has been shown to cleave translated mRNAs and through this mechanism to block protein synthesis within prokaryotic cells. MazEF has been found to be an important TA system in a variety of prokaryotes including E. coli, S. aureus, and S. pneumonia.
Dartmouth scientists have now identified the cleavage site of mRNA that is attacked by MazF in S. aureus. Based upon this finding, a hybrid RNA-DNA molecule was developed, which contains a fluorescent tag at one end and quencher at the other end. The resulting RNA-DNA hybrid molecule fails to yield significant fluorescence unless the RNA target site is cleaved by the MazF toxin to separate the fluorescent tag from the quencher. This hybrid molecule was used in antibiotic screening assays and compounds that disrupt the MazEF complex were identified. These compounds were further analyzed and shown to inhibit the growth of S. aureus in vitro. Therefore, these compounds, as well as analogs and derivatives thereof, can be used in the treatment of S. aureus infections.
These findings are claimed in the published PCT patent application Nos. PCT/US2010/040695 and PCT/US2010/040696. We are seeking an industrial partner to further refine and market this technology. (Ref: J538)
Last Updated: 7/24/12