Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane

Annabelle Gallois; Joanna R Klein; Lee-Ann H Allen; Bradley D Jones; William M Nauseef

doi:10.4049/jimmunol.166.9.5741

Back

Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane

Journal article

Open access

Peer reviewed

Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane

Annabelle Gallois, Joanna R Klein, Lee-Ann H Allen, Bradley D Jones and William M Nauseef

The Journal of immunology (1950), Vol.166(9), pp.5741-5748

05/01/2001

DOI: 10.4049/jimmunol.166.9.5741

PMID: 11313417

View Online

Abstract

Salmonella typhimurium requires a type III secretion system encoded by pathogenicity island (SPI)-2 to survive and proliferate within macrophages. This survival implies that S. typhimurium avoids or withstands bactericidal events targeted to the microbe-containing vacuole, which include intraphagosomal production of reactive oxygen species (ROS), phagosomal acidification, and delivery of hydrolytic enzymes to the phagosome via fusion with lysosomes. Recent evidence suggests that S. typhimurium alters ROS production by murine macrophages in an SPI-2-dependent manner. To gain insights into the mechanism by which S. typhimurium inhibits intraphagosomal ROS production, we analyzed the subcellular distribution of NADPH oxidase components during infection of human monocyte-derived macrophages by wild-type (WT) or several SPI-2 mutant strains of S. typhimurium. We found that the membrane component of the NADPH oxidase, flavocytochrome b(558), was actively excluded or rapidly removed from the phagosomal membrane of WT-infected monocyte-derived macrophages, thereby preventing assembly of the NADPH oxidase complex and intraphagosomal production of superoxide anion. In contrast, the NADPH oxidase assembled on and generated ROS in phagosomes containing SPI-2 mutant S. typhimurium. Subversion of NADPH oxidase assembly by S. typhimurium was accompanied by increased bacterial replication relative to that of SPI-2 mutant strains, suggesting that the ability of WT S. typhimurium to prevent NADPH oxidase assembly at the phagosomal membrane represents an important virulence factor influencing its intracellular survival.

Phenotype

Mutagenesis

Phagosomes - microbiology

Intracellular Membranes - enzymology

Phagosomes - enzymology

Salmonella typhimurium - growth & development

Humans

NADPH Oxidases - metabolism

Phosphoproteins - metabolism

Cytochrome b Group - metabolism

Superoxides - metabolism

Adult

Female

Intracellular Membranes - microbiology

Macrophages - microbiology

Salmonella typhimurium - genetics

Salmonella typhimurium - pathogenicity

NADPH Oxidases - antagonists & inhibitors

Phagosomes - metabolism

Macrophages - enzymology

Macrophages - metabolism

Animals

Phosphoproteins - deficiency

Cytochrome b Group - deficiency

Mice

Intracellular Membranes - metabolism

Phagosomes - genetics

Details

Title: Subtitle: Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane
Creators: Annabelle Gallois - The Inflammation Program and Department of Medicine, University of Iowa and the Veterans' Affairs Medical Center, Iowa City, IA 52242, USA
Joanna R Klein
Lee-Ann H Allen
Bradley D Jones
William M Nauseef
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.166(9), pp.5741-5748
DOI: 10.4049/jimmunol.166.9.5741
PMID: 11313417
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI94789-13 / NIAID NIH HHS I01 BX000513 / BLRD VA AI38268 / NIAID NIH HHS
Language: English
Date published: 05/01/2001
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984083843302771

Metrics

15 Record Views

181 Times Cited - Web of Science