S-Space College of Medicine/School of Medicine (의과대학/대학원) Microbiology (미생물학전공) Journal Papers (저널논문_미생물학전공)
Intracellular Invasion by Orientia tsutsugamushi Is Mediated by Integrin Signaling and Actin Cytoskeleton Rearrangements
Cited 47 time in Web of Science Cited 51 time in Scopus
- Issue Date
- AMER SOC MICROBIOLOGY
- INFECTION AND IMMUNITY; Vol.78 5; 1915-1923
- 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 alpha 5 beta 1 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.
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