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Intracellular Invasion by Orientia tsutsugamushi Is Mediated by Integrin Signaling and Actin Cytoskeleton Rearrangements
- Source :
- Infection and Immunity. 78:1915-1923
- Publication Year :
- 2010
- Publisher :
- American Society for Microbiology, 2010.
-
Abstract
- Orientia tsutsugamushi , the causative agent of scrub typhus, is an obligate intracellular pathogen. Previously, we reported that the 56-kDa type-specific antigen (TSA56), a major outer membrane protein of O. tsutsugamushi , binds to fibronectin and facilitates bacterial entry into the host cell, potentially via an interaction with integrins. Here, we demonstrated that O. tsutsugamushi colocalizes with integrin α5β1 and activates integrin signaling effectors, including focal adhesion kinase, Src kinase, and RhoA GTPase, and also recruits signaling adaptors, such as talin and paxillin, to the site of infection. Inhibition of protein tyrosine kinases or RhoA reduced intracellular invasion. We also observed substantial actin reorganization and membrane protrusions at the sites of infection of nonphagocytic host cells. Finally, we identified a region in the extracellular domain of TSA56 that binds to fibronectin. A peptide containing this region was able to significantly reduce bacterial invasion. Taken together, these results clearly indicate that O. tsutsugamushi exploits integrin-mediated signaling and the actin cytoskeleton for invasion of eukaryotic host cells.
- Subjects :
- Talin
RHOA
Orientia tsutsugamushi
Immunology
Integrin
Microbiology
Cell Line
Focal adhesion
Mice
Animals
Humans
Protein Interaction Domains and Motifs
Cytoskeleton
Paxillin
Antigens, Bacterial
Microscopy, Confocal
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
biology
bacterial infections and mycoses
Actin cytoskeleton
biology.organism_classification
Molecular biology
Endocytosis
Cell biology
src-Family Kinases
Infectious Diseases
biology.protein
Parasitology
Bacterial antigen
rhoA GTP-Binding Protein
Integrin alpha5beta1
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 10985522 and 00199567
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- Infection and Immunity
- Accession number :
- edsair.doi.dedup.....7ada2ad36e46c72ce1bbd89bacfb9325