Hijacking the Ubl code: bacterial manipulation of ubiquitin-like proteins.

Ubiquitin (Ub) and Ub-like (Ubl) signaling processes regulate broad aspects of eukaryotic cellular biology. Conserved sets of enzymes control the covalent attachment of Ub/Ubl onto proteins, and disruption of these highly regulated processes contributes to diseases including cancer and neurodegeneration. Aspects of Ub/Ubl signaling are central to the innate immune response to infectious pathogens. As such, pathogens such as viruses and bacteria have evolved sophisticated mechanisms to hijack and dysregulate the homeostasis of Ub/Ubl signaling. Pathogenic manipulation of the host Ub system is well studied, with multiple classes of secreted bacterial effector proteins discovered that regulate either Ub itself or the enzymes required for substrate ubiquitylation. While much less is known about the control of host Ubl signaling processes by pathogens, recent discoveries indicate that they, too, are hijacked during infection. The number of Ubl manipulators secreted by bacterial pathogens is likely to increase in the coming years as methods to identify and characterize bacterial effectors advance. This review highlights the current knowledge on bacterial manipulation of Ubl signaling, including SUMO, NEDD8, ISG15, UFM1, FAT10, and LC3.