Journal Article

Legionella longbeachae effector protein RavZ inhibits autophagy and regulates phagosome ubiquitination during infection

Ma, Kelong, Qiu, Jiazhang, Liu, Hongtao, Shi, Yunjia, Luo, Zhao-Qing

2023

Overview

Legionella organisms are ubiquitous environmental bacteria that are responsible for human Legionnaires’ disease, a fatal form of severe pneumonia. These bacteria replicate intracellularly in a wide spectrum of host cells within a distinct compartment termed the L egionella - c ontaining v 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 L . pneumophila 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 LP ) ortholog in L . longbeachae (RavZ LLO ), the second leading cause of Legionella infections in the world. RavZ LLO and RavZ LP share approximately 60% sequence identity and a conserved His-Asp-Cys catalytic triad. RavZ LLO is recognized by the Dot/Icm systems of both L . pneumophila and L . longbeachae . Upon translocation into the host, it suppresses autophagy signaling in cells challenged with both species, indicating the functional redundancy of RavZ LLO and RavZ LP . Additionally, ectopic expression of RavZ LLO but not RavZ LP in mammalian cells reduces the levels of cellular polyubiquitinated and polyneddylated proteins. Consistent with this process, RavZ LLO regulates the accumulation of polyubiquitinated species on the LCV during L . longbeachae infection.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Autophagy / Bacteria / Bacterial diseases / Bacterial infections / Bacterial Proteins - genetics / Biology and Life Sciences / Cell death / Cells / Cloning / Conserved sequence / Cysteine proteinase / Diagnosis / E coli / Ectopic expression / Gene expression / Genetic engineering / Health aspects / Humans / Infection / Infections / Legionella / Legionella longbeachae - metabolism / Legionella pneumophila / Legionnaire's disease / Legionnaires' disease / Legionnaires' Disease - microbiology / Mammalian cells / Mammals - metabolism / Medical research / Medicine and Health Sciences / Medicine, Experimental / Pathogenesis / Phagosomes - metabolism / Plasmids / Proteins / Redundancy / Research and Analysis Methods / Risk factors / Translocation / Ubiquitin / Ubiquitination / Vacuoles - metabolism