Orthogonal Prokaryotic Transcription as a Platform for Antibiotic Screening
Bacterial RNA polymerases (RNAPs) are a promising target for antibiotics. However, screening is often hampered by culture conditions, generation time, biosafety considerations, and poorly understood mechanisms of action. We propose an orthogonal, interspecies transcription system for the screening of large drug libraries against functional RNAPs from diverse, clinically relevant bacteria in E. coli. As well as providing a direct mechanism of action, this platform may enable the discovery of narrow spectrum RNAP inhibitors.