The Salmonella LysR Family Regulator RipR Activates the SPI-13-Encoded Itaconate Degradation Cluster

Abstract

Itaconate is a dicarboxylic acid that inhibits the isocitrate lyase enzyme of the bacterial glyoxylate shunt. Activated macrophages have been shown to produce itaconate, suggesting that these immune cells may employ this metabolite as a weapon against invading bacteria. Here, we demonstrate that in vitro , itaconate can exhibit bactericidal effects under acidic conditions similar to the pH of a macrophage phagosome. In parallel, successful pathogens, including Salmonella , have acquired a genetic operon encoding itaconate degradation proteins, which are induced heavily in macrophages.