Chlamydia trachomatis is the most frequently diagnosed pathogen of sexually transmitted diseases worldwide, with more than 120 million new cases reported in 2020. During the establishment of a successful infection, subversion of the host cell autonomous immune response is a major challenge for obligate intracellular bacteria. In this context, ubiquitinylation plays a key role in both autophagic processes and proteasomal degradation of bacterial proteins. The chlamydial deubiquitinase Cdu1 is anchored to the inclusion membrane with its active site facing the host cell cytosol and is capable of reversing ubiquitin-based decoration of the inclusion surface. We have identified the responsible host E3 ligase and are currently investigating another example of the intricate cross-regulation between the eukaryotic ubiquitin machinery and chlamydial DUBs.