Researchers develop a dual mechanism to defeat antibiotic-resistant bacteria

A team of Princeton researchers reported in the journal Cell that they have found a compound (SCH-79797), that kills both Gram-negative and Gram-positive bacteria. The killing mechanism is through a unique dual-targeting mechanism of action (MoA) with undetectably low resistance frequencies. They demonstrated that SCH-79797 has two independent cellular targets, folate metabolism, and bacterial membrane integrity, and outperforms combination treatments in killing methicillin-resistant Staphylococcus aureus (MRSA) persisters. Building on the molecular core of SCH-79797, they developed a derivative, Irresistin-16, with increased potency and showed its efficacy against Neisseria gonorrhoeae in a mouse vaginal infection model. The Princeton team found that even with extraordinary effort, they were unable to generate any resistance to this compound. This promising antibiotic suggests that combining multiple MoAs onto a single chemical may be an underappreciated approach to targeting antibiotic-resistant bacteria. @ https://doi.org/10.1016/j.cell.2020.05.005