Small molecule resensitizes Salmonella to itaconate and decreases bacterial proliferation in macrophages

Abstract

Antimicrobial resistance is a global health crisis offering little reprieve. The situation urgently calls for new drug targets and therapies for infections. We have previously suggested a different approach to treat infections, termed bacterio-modulation, in which a compound modulates the bacterial response to the host immune defense. Herein we show that monocytes infected with Salmonella enterica spp. Typhimurium can be cured using non-antimicrobial compounds that resensitize the bacterium to itaconate, a macrophage-derived antimicrobial metabolite. We propose that this represents a novel strategy to treat infections.