Itaconate: an antimicrobial metabolite of macrophages

Abstract

Itaconate is a conjugated 1,4-dicarboxylate produced by macrophages. This small molecule has recently received increasing attention due to its role in modulating the immune response of macrophages upon exposure to pathogens. Itaconate has also been proposed to play an antimicrobial function; however, this has not been explored as intensively. Consistent with the latter, itaconate is known to show antibacterial activity in vitro and was reported to inhibit isocitrate lyase, an enzyme required for survival of bacterial pathogens in mammalian systems. Recent studies have revealed bacterial growth inhibition under biologically relevant conditions. In addition, an antimicrobial role for itaconate is substantiated by the high concentration of itaconate found in bacteria-containing vacuoles, and by the production of itaconate-degrading enzymes in pathogens such as Salmonella enterica ser. Typhimurium, Pseudomonas aeruginosa, and Yersinia pestis. This review describes the current state of literature in understanding the role of itaconate as an antimicrobial agent in host–pathogen interactions.