Infections with bacterial pathogens represent a global burden and are a major cause of death worldwide. For the design of new treatment paradigms it is essential to understand the intricate interplay between bacterial virulence strategies and host defense. The Dikic laboratory now added the next piece to the puzzle: They elucidated how the Salmonella effector enzyme SopA, a HECT-like E3 ligase, targets two host proteins involved in activating the immune defense (TRIM56 and TRIM65) and triggers their degradation. Atomic details of this new mechanism have now been published in Nature Communications and give a detailed insight into how Salmonella increases its own infectivity by interfering with the host immune response.