The Salmonella-containing vacuole is a major site of intracellular cholesterol accumulation and recruits the GPI-anchored protein CD55

Drew M Catron; Matthew D Sylvester; Yvonne Lange; Madhusudan Kadekoppala; Bradley D Jones; Denise M Monack; Stanley Falkow; Kasturi Haldar

doi:10.1046/j.1462-5822.2002.00198.x

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The Salmonella-containing vacuole is a major site of intracellular cholesterol accumulation and recruits the GPI-anchored protein CD55

Journal article

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The Salmonella-containing vacuole is a major site of intracellular cholesterol accumulation and recruits the GPI-anchored protein CD55

Drew M Catron, Matthew D Sylvester, Yvonne Lange, Madhusudan Kadekoppala, Bradley D Jones, Denise M Monack, Stanley Falkow and Kasturi Haldar

Cellular microbiology, Vol.4(6), pp.315-328

06/2002

DOI: 10.1046/j.1462-5822.2002.00198.x

PMID: 12067317

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Abstract

Intracellular, pathogenic Salmonella typhimurium avoids phago-lysosome fusion, and exists within a unique vacuolar niche that resembles a late endosome. This model has emerged from studying the trafficking of host proteins to the Salmonella-containing vacuole (SCV). Very little is known about the role of major host lipids during infection. Here, we show using biochemical analyses as well as fluorescence microscopy, that intracellular infection perturbs the host sterol biosynthetic pathway and induces cholesterol accumulation in the SCV. Cholesterol accumulation is seen in both macrophages and epithelial cells: at the terminal stages of infection, as much as 30% of the total cellular cholesterol resides in the SCV. We find that accumulation of cholesterol in the SCV is linked to intracellular bacterial replication and may be dependent on Salmonella pathogenicity island 2 (SPI-2). Furthermore, the construction of a three-dimensional space-filling model yields novel insights into the structure of the SCV: bacteria embedded in cholesterol-rich membranes. Finally, we show that the glycosylphosphatidylinositol (GPI)-anchored protein CD55 is recruited to the SCV. These data suggest that, in contrast to prevailing models, the SCV accumulates components of cholesterol-rich early endocytic pathways during intracellular bacterial replication.

Signal Transduction

Vacuoles - microbiology

Salmonella typhimurium - growth & development

Sterols - analysis

Filipin - analysis

Cholesterol - metabolism

Macrophages - metabolism

Animals

Glycosylphosphatidylinositols - metabolism

Vacuoles - metabolism

CD55 Antigens - metabolism

Lanosterol - metabolism

Mice

Details

Title: Subtitle: The Salmonella-containing vacuole is a major site of intracellular cholesterol accumulation and recruits the GPI-anchored protein CD55
Creators: Drew M Catron - Departments of Pathology and Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA
Matthew D Sylvester
Yvonne Lange
Madhusudan Kadekoppala
Bradley D Jones
Denise M Monack
Stanley Falkow
Kasturi Haldar
Resource Type: Journal article
Publication Details: Cellular microbiology, Vol.4(6), pp.315-328
DOI: 10.1046/j.1462-5822.2002.00198.x
PMID: 12067317
ISSN: 1462-5814
eISSN: 1462-5822
Grant note: 5T32GM08061 / NIGMS NIH HHS HL28448 / NHLBI NIH HHS
Language: English
Date published: 06/2002
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083810702771

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