Salmonella-Containing Vacuoles Display Centrifugal Movement Associated with Cell-to-Cell Transfer in Epithelial Cells▿
| Autor: | Jason Szeto, Anton Namolovan, John H. Brumell, Suzanne E. Osborne, Brian K. Coombes |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Immunology
Fluorescent Antibody Technique Kinesins Vacuole Cell Communication Biology Transfection Microbiology Bacterial Proteins Host cell periphery Humans Secretion Cytoskeleton Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Effector Membrane Proteins Salmonella enterica Epithelial Cells biochemical phenomena metabolism and nutrition biology.organism_classification bacterial infections and mycoses Infectious Diseases Membrane protein Salmonella Infections Vacuoles bacteria Parasitology Intracellular HeLa Cells |
| Popis: | Intracellular Salmonella enterica serovar Typhimurium (serovar Typhimurium) occupies a Salmonella -containing vacuole (SCV) where bacterial effector proteins are secreted into the host cell using type III secretion systems (T3SS). Cytoskeletal motor proteins and T3SS-delivered effector proteins facilitate SCV positioning to juxtanuclear positions where bacterial replication occurs. Here, we show that this characteristic SCV positioning is not maintained by all SCVs during infection of HeLa cells. Notably, juxtanuclear SCV localization that occurs by 8 to 14 h postinfection is followed by significant centrifugal displacement of a subset of SCVs toward the host cell periphery by 24 h postinfection. This novel phenotype requires bacterial protein synthesis, a functional Salmonella pathogenicity island 2 (SPI-2)-encoded T3SS, intact microtubules, and kinesin-1 motor protein. Bacteria lacking PipB2, a kinesin-recruiting T3SS effector, did not exhibit centrifugal displacement and remained at juxtanuclear positions throughout 24 h of infection. While levels of the SPI-2 effectors PipB2 and SifA increased during 24 h postinfection, a corresponding decrease in levels of the SPI-1 T3SS effectors SipA and SopB, both known to mediate juxtanuclear SCV positioning, was observed. A fluorescence-based assay indicated that wild-type serovar Typhimurium transferred from infected to uninfected epithelial cells while strains deficient in SPI-2 T3SS secretion or PipB2 did not. Our results reveal a novel SCV phenotype implicated in the cell-to-cell spread of serovar Typhimurium during infection. |
| Databáze: | OpenAIRE |
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