Update information. We utilized a large-scale proteomic profiling strategy to quantitatively measure ADP-riboxanation (and classical ADP-ribosylation) levels of host proteins upon introduction of bacterial effectors. Notably, we identified the eukaryotic translation initiation factor 3 (eIF3) complex as a novel target of the OspC family proteins. ADP-riboxanation of eIF3 resulted in inhibition of bulk protein synthesis and SG assembly in infected host cells, which promoted intracellular bacterial proliferation.