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To infect cells,\n            <jats:italic>Ehrlichia<\/jats:italic>\n            uses the\n            <jats:underline>C<\/jats:underline>\n            terminus of the outer membrane invasin\n            <jats:underline>e<\/jats:underline>\n            ntry-\n            <jats:underline>t<\/jats:underline>\n            riggering\n            <jats:underline>p<\/jats:underline>\n            rotein (EtpE) of\n            <jats:italic>Ehrlichia<\/jats:italic>\n            (EtpE-C), which directly binds the mammalian cell surface glycosylphosphatidyl inositol-anchored protein, DNase X. How this binding drives\n            <jats:italic>Ehrlichia<\/jats:italic>\n            entry is unknown. Here, using affinity pulldown of host cell lysates with recombinant EtpE-C (rEtpE-C), we identified two new human proteins that interact with EtpE-C: CD147 and heterogeneous nuclear ribonucleoprotein K (hnRNP-K). The interaction of CD147 with rEtpE-C was validated by far-Western blotting and coimmunoprecipitation of native EtpE with endogenous CD147. CD147 was ubiquitous on the cell surface and also present around foci of rEtpE-C-coated-bead entry. Functional neutralization of surface-exposed CD147 with a specific antibody inhibited\n            <jats:italic>Ehrlichia<\/jats:italic>\n            internalization and infection but not binding. Downregulation of CD147 by short hairpin RNA (shRNA) impaired\n            <jats:italic>E.\u00a0chaffeensis<\/jats:italic>\n            infection. Functional ablation of cytoplasmic hnRNP-K by a nanoscale intracellular antibody markedly attenuated bacterial entry and infection but not binding. EtpE-C also interacted with neuronal Wiskott-Aldrich syndrome protein (N-WASP), which is activated by hnRNP-K. Wiskostatin, which inhibits N-WASP activation, and cytochalasin D, which inhibits actin polymerization, inhibited\n            <jats:italic>Ehrlichia<\/jats:italic>\n            entry. Upon incubation with host cell lysate, EtpE-C but not an EtpE N-terminal fragment stimulated\n            <jats:italic>in vitro<\/jats:italic>\n            actin polymerization in an N-WASP- and DNase X-dependent manner. Time-lapse video images revealed N-WASP recruitment at EtpE-C-coated bead entry foci. Thus, EtpE-C binding to DNase X drives\n            <jats:italic>Ehrlichia<\/jats:italic>\n            entry by engaging CD147 and hnRNP-K and activating N-WASP-dependent actin polymerization.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">Ehrlichia chaffeensis<\/jats:named-content>\n            , an obligate intracellular bacterium, causes a blood-borne disease called human monocytic ehrlichiosis, one of the most prevalent life-threatening emerging tick-transmitted infectious diseases in the United States. The survival of\n            <jats:italic>Ehrlichia<\/jats:italic>\n            bacteria, and hence, their ability to cause disease, depends on their specific mode of entry into eukaryotic host cells. Understanding the mechanism by which\n            <jats:italic>E.\u00a0chaffeensis<\/jats:italic>\n            enters cells will create new opportunities for developing effective therapies to prevent bacterial entry and disease in humans. Our findings reveal a novel cellular signaling pathway triggered by an ehrlichial surface protein called EtpE to induce its infectious entry. The results are also important from the viewpoint of human cell physiology because three EtpE-interacting human proteins, DNase X, CD147, and hnRNP-K, are hitherto unknown partners that drive the uptake of small particles, including bacteria, into human cells.\n          <\/jats:p>","DOI":"10.1128\/mbio.01541-15","type":"journal-article","created":{"date-parts":[[2015,11,4]],"date-time":"2015-11-04T02:34:47Z","timestamp":1446604487000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["EtpE Binding to DNase X Induces Ehrlichial Entry via CD147 and hnRNP-K Recruitment, Followed by Mobilization of N-WASP and Actin"],"prefix":"10.1128","volume":"6","author":[{"given":"Dipu","family":"Mohan Kumar","sequence":"first","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingqun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingming","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathew James","family":"Webber","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Comert","family":"Kural","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, Ohio, USA"},{"name":"Department of Physics, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuko","family":"Rikihisa","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"CDC. 2015. 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