Exploration of BAY 11-7082 as a Potential Antibiotic
Victoria E. Coles, Patrick Darveau, Xiong Zhang, Hanjeong Harvey, Brandyn D. Henriksbo, Angela Yang, Jonathan D. Schertzer, Jakob Magolan, Lori L. Burrows
Abstract
activity. Because the parent molecule inhibits the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome, we measured the ability of select analogues to reduce interleukin-1β (IL-1β) production in mammalian macrophages, identifying minor differences in the structure-activity relationship for the anti-inflammatory and antibacterial properties of this scaffold. Although we could evolve stably resistant MRSA mutants with cross-resistance to BAY 11-7082 and PSPC, their lack of shared mutations suggested that the two molecules could have multiple targets. Finally, we showed that BAY 11-7082 and its analogues synergize with penicillin G against MRSA, suggesting that this scaffold may serve as an interesting starting point for the development of antibiotic adjuvants.