Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector

PLoS Pathogens

Zhao-Qing Luo¹  Xihui Shen¹  Li Xu¹  Simran Banga¹  Michele S. Swanson²  Andrew Bryan² 

[1] Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America;Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

关键词: Legionella pneumophila;    Yeast;    Macrophages;    Immunoprecipitation;    Protons;    Phagosomes;    Vacuoles;    Vesicles;   

DOI  :  10.1371/journal.ppat.1000822

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Legionella pneumophila is an intracellular pathogen responsible for Legionnaires' disease. This bacterium uses the Dot/Icm type IV secretion system to inject a large number of bacterial proteins into host cells to facilitate the biogenesis of a phagosome permissive for its intracellular growth. Like many highly adapted intravacuolar pathogens, L. pneumophila is able to maintain a neutral pH in the lumen of its phagosome, particularly in the early phase of infection. However, in all cases, the molecular mechanisms underlying this observation remain unknown. In this report, we describe the identification and characterization of a Legionella protein termed SidK that specifically targets host v-ATPase, the multi-subunit machinery primarily responsible for organelle acidification in eukaryotic cells. Our results indicate that after being injected into infected cells by the Dot/Icm secretion system, SidK interacts with VatA, a key component of the proton pump. Such binding leads to the inhibition of ATP hydrolysis and proton translocation. When delivered into macrophages, SidK inhibits vacuole acidification and impairs the ability of the cells to digest non-pathogenic E. coli. We also show that a domain located in the N-terminal portion of SidK is responsible for its interactions with VatA. Furthermore, expression of sidK is highly induced when bacteria begin to enter new growth cycle, correlating well with the potential temporal requirement of its activity during infection. Our results indicate that direct targeting of v-ATPase by secreted proteins constitutes a virulence strategy for L. pneumophila, a vacuolar pathogen of macrophages and amoebae.

【 授权许可】

CC BY