Rickettsial outer-membrane protein B (rOmpB) mediates bacterial invasion through Ku70 in an actin, c-Cbl, clathrin and caveolin 2-dependent manner
| Autor: | Timothy M. Hermanas, Yvonne G. Y. Chan, Juan J. Martinez, Tsuneo Uchiyama, Marissa M. Cardwell |
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| Rok vydání: | 2009 |
| Předmět: |
Caveolin 2
media_common.quotation_subject Immunology Endocytic cycle Biology Microbiology Clathrin Article Virology Chlorocebus aethiops Animals Humans Proto-Oncogene Proteins c-cbl Internalization Ku Autoantigen Vero Cells Actin media_common Antigens Nuclear Epithelial Cells Molecular biology Actins Cell biology DNA-Binding Proteins Rickettsia conorii Host-Pathogen Interactions Autotransporter domain biology.protein Bacterial outer membrane Tyrosine kinase Bacterial Outer Membrane Proteins HeLa Cells |
| Zdroj: | Cellular Microbiology. 11:629-644 |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/j.1462-5822.2008.01279.x |
| Popis: | Rickettsia conorii, an obligate intracellular tick-borne pathogen and the causative agent of Mediterranean spotted fever, binds to and invades non-phagocytic mammalian cells. Previous work identified Ku70 as a mammalian receptor involved in the invasion process and identified the rickettsial autotransporter protein, rOmpB, as a ligand; however, little is known about the role of Ku70-rOmpB interactions in the bacterial invasion process. Using an Escherichia coli heterologous expression system, we show here that rOmpB mediates attachment to mammalian cells and entry in a Ku70-dependent process. A purified recombinant peptide corresponding to the rOmpB passenger domain interacts with Ku70 and serves as a competitive inhibitor of adherence. We observe that rOmpB-mediated infection culminates in actin recruitment at the bacterial foci, and that this entry process relies in part on actin polymerization likely imparted through protein tyrosine kinase and phosphoinositide 3-kinase-dependent activities and microtubule stability. Small-interfering RNA studies targeting components of the endocytic pathway reveal that entry by rOmpB is dependent on c-Cbl, clathrin and caveolin-2. Together, these results illustrate that rOmpB is sufficient to mediate Ku70-dependent invasion of mammalian cells and that clathrin- and caveolin-dependent endocytic events likely contribute to the internalization process. |
| Databáze: | OpenAIRE |
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