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These bacteria replicate intracellularly in a wide spectrum of host cells within a distinct compartment termed the<jats:underline><jats:italic>L<\/jats:italic><\/jats:underline><jats:italic>egionella<\/jats:italic>-<jats:underline>c<\/jats:underline>ontaining<jats:underline>v<\/jats:underline>acuole (LCV). Effector proteins translocated by the Dot\/Icm apparatus extensively modulate host cellular functions to aid in the biogenesis of the LCV and intracellular proliferation. RavZ is an<jats:italic>L<\/jats:italic>.<jats:italic>pneumophila<\/jats:italic>effector that functions as a cysteine protease to hydrolyze lipidated LC3, thereby compromising the host autophagic response to bacterial infection. In this study, we characterized the RavZ (RavZ<jats:sub>LP<\/jats:sub>) ortholog in<jats:italic>L<\/jats:italic>.<jats:italic>longbeachae<\/jats:italic>(RavZ<jats:sub>LLO<\/jats:sub>), the second leading cause of<jats:italic>Legionella<\/jats:italic>infections in the world. RavZ<jats:sub>LLO<\/jats:sub>and RavZ<jats:sub>LP<\/jats:sub>share approximately 60% sequence identity and a conserved His-Asp-Cys catalytic triad. RavZ<jats:sub>LLO<\/jats:sub>is recognized by the Dot\/Icm systems of both<jats:italic>L<\/jats:italic>.<jats:italic>pneumophila<\/jats:italic>and<jats:italic>L<\/jats:italic>.<jats:italic>longbeachae<\/jats:italic>. Upon translocation into the host, it suppresses autophagy signaling in cells challenged with both species, indicating the functional redundancy of RavZ<jats:sub>LLO<\/jats:sub>and RavZ<jats:sub>LP<\/jats:sub>. Additionally, ectopic expression of RavZ<jats:sub>LLO<\/jats:sub>but not RavZ<jats:sub>LP<\/jats:sub>in mammalian cells reduces the levels of cellular polyubiquitinated and polyneddylated proteins. Consistent with this process, RavZ<jats:sub>LLO<\/jats:sub>regulates the accumulation of polyubiquitinated species on the LCV during<jats:italic>L<\/jats:italic>.<jats:italic>longbeachae<\/jats:italic>infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0281587","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T18:44:09Z","timestamp":1675968249000},"page":"e0281587","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Legionella longbeachae effector protein RavZ inhibits autophagy and regulates phagosome ubiquitination during 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