Ubiquitination is a post-translational modification in which ubiquitin, a 76 amino acid polypeptide, is covalently bound to one or more lysines of a target protein. Ubiquitination is mediated by the coordinated activity of ubiquitin activating (E1), conjugating (E2), and ligating (E3) enzymes. Ubiquitin is widely investigated for its ability to regulate key biological processes in the cell, including protein degradation and host-bacteria interactions. The determinants underlying bacterial ubiquitination, and their precise roles in host defense, have not been fully resolved. In this issue of EMBO reports, Polajnar et al discover that Ring-between-Ring (RBR) E3 ligase ARIH1 (also known as HHARI) is involved in formation of the ubiquitin coat surrounding cytosolic Salmonella [1]. Evidence suggests that ARIH1, in cooperation with E3 ligases LRSAM1 and HOIP, modulates the recognition of intracellular bacteria for cellautonomous immunity.