Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella

Rab32 puts itaconate where it's needed Myeloid cells can restrict the replication of intracellular bacterial pathogens such as Salmonella using a Rab family guanosine triphosphatase called Rab32. However, the underlying mechanisms remain unclear. Chen et al. report that Rab32 and its exchange factor, BLOC3, interact with aconitate decarboxylase 1 (IRG1). This complex enables the direct delivery of IRG1's antimicrobial product, itaconate, from the mitochondria to Salmonella -containing vacuoles. Itaconate concentrations in vacuoles correlated with bacterial survival, highlighting the biological relevance of this metabolite during infections. Similar findings in Escherichia coli –infected cells suggest that this is a more general phenomenon in which mitochondria and the Rab32 pathway play a critical role in antibacterial host defense. Science , this issue p. 450