Methods for screening antibiotic compounds

A synthetic substrate comprising a MazF recognition site (AUUC) flanked on either side by at least four deoxyribonucleotides, wherein said substrate comprises a fluorescence marker at one end and a quencher at the other end.

A method of screening a drug for activity to disrupt a toxin-antitoxin complex in a whole cell bacterial cell assay comprising contacting a bacterial cell expressing a wild-type toxin-antitoxin complex with a test drug, contacting a bacterial which does not express the toxin-antitoxin complex with the test drug, and determining whether the test drug reduces the growth of the bacterial cell expressing the wild-type toxin-antitoxin complex as compared to the growth of the bacterial cell which does not express the toxin-antitoxin complex, wherein a reduction in bacterial growth is indicative of activity to disrupt a toxin-antitoxin complex in the wild-type bacterial cell.

A method of screening a drug for efficacy as an antibiotic comprising inoculating a first mouse with a bacterial strain expressing a wild-type toxin-antitoxin complex, inoculating a second mouse with a bacterial strain which does not express the toxin-antitoxin complex, administering to both the first mouse and the second mouse a test drug and measuring a volume of bacterial abscess that forms subcutaneously on said first mouse and said second mouse, wherein a reduction in said bacterial abscess volume or number of bacteria in the first mouse when compared with abscess volume or number of bacteria in the second mouse is indicative of efficacy of the test drug as an antibiotic compound.