We take an interdisciplinary approach combining cutting-edge proteomics with genome editing, biochemistry and cellular microbiology to determine fundamental properties and modes of action of understudied ubiquitin-like modifications. We aim to address the fundamental question of how the cell responds to stress by decoding novel networks of covalent protein complexes. As a model, we compare infection with two intracellular pathogens: Listeria monocytogenes and Francisella tularensis.