Novel Antimicrobial Agent Development from Unprecedented Targets

. Structure-Based Drug Design from Protein-Protein Interactions (PPIs) in Bacterial Transcription .

Bacterial infections are causing re-emerging epidemics invasive to human health and global economy due to antimicrobial resistance (AMR). To solve this problem, we focus on studying an underutilized drug target, bacterial transcription responsible for RNA synthesis to develop first-in-class antimicrobial agents. Structure-based drug design (SBDD) strategy was used for screen-to-hit identification targeting proteinprotein interactions (PPIs) in bacterial transcription as unprecedented drug targets. Current lead compounds as the inhibitors of various PPIs are being optimized to show potent antibacterial activity against clinical pathogenic species such as methicillin-resistant Staphylococcus aureus(MRSA), Clostridium difficile, Acinetobacter baumannii and Escherichia coli. These compounds demonstrated drug-like pharmacokinetic properties, low toxicity, and no AMR generation in 30-day serial passage experiments.

Novel-Antimicrobial-Agent-Development-from-Unprecedented-Targets

Principal Investigator

Dr. Cong MA
Department of Applied Biology and Chemical Technology

Representative Publications

Yang X, Luo MJ, Yeung ACM, Lewis PJ, Chan PKS, Ip M, Ma C. (2017) First-In-Class Inhibitor of Ribosomal RNA Synthesis with Antimicrobial Activity against Staphylococcus aureus. Biochemistry 56, 5049-5052.
Ma C, Yang X, Lewis PJ. (2016) Bacterial Transcription as a Target for Antibacterial Drug Development. Microbiology and Molecular Biology Reviews 80, 139- 160.
Ma C, Yang X, Lewis PJ. (2016) Bacterial Transcription Inhibitor of RNA Polymerase Holoenzyme Formation by Structure-Based Drug Design: From in Silico Screening to Validation. ACS Infectious Diseases 2, 39-46.