Helicobacter pylori VacA toxin promotes bacterial intracellular survival in gastric epithelial cells.

Abstract:

:Helicobacter pylori colonizes the gastric epithelium of at least 50% of the world's human population, playing a causative role in the development of chronic gastritis, peptic ulcers, and gastric adenocarcinoma. Current evidence indicates that H. pylori can invade epithelial cells in the gastric mucosa. However, relatively little is known about the biology of H. pylori invasion and survival in host cells. Here, we analyze both the nature of and the mechanisms responsible for the formation of H. pylori's intracellular niche. We show that in AGS cells infected with H. pylori, bacterium-containing vacuoles originate through the fusion of late endocytic organelles. This process is mediated by the VacA-dependent retention of the small GTPase Rab7. In addition, functional interactions between Rab7 and its downstream effector, Rab-interacting lysosomal protein (RILP), are necessary for the formation of the bacterial compartment since expression of mutant forms of RILP or Rab7 that fail to bind each other impaired the formation of this unique bacterial niche. Moreover, the VacA-mediated sequestration of active Rab7 disrupts the full maturation of vacuoles as assessed by the lack of both colocalization with cathepsin D and degradation of internalized cargo in the H. pylori-containing vacuole. Based on these findings, we propose that the VacA-dependent isolation of the H. pylori-containing vacuole from bactericidal components of the lysosomal pathway promotes bacterial survival and contributes to the persistence of infection.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Terebiznik MR,Vazquez CL,Torbicki K,Banks D,Wang T,Hong W,Blanke SR,Colombo MI,Jones NL

doi

10.1128/IAI.01085-06

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

6599-614

issue

12

eissn

0019-9567

issn

1098-5522

pii

IAI.01085-06

journal_volume

74

pub_type

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