{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:45:55Z","timestamp":1793321155403,"version":"4.5.0"},"reference-count":166,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Maryland Agricultural Research Station"},{"name":"Ann G Wylie Dissertation Fellowship"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2025,10,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Bacteria in the genus\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      are obligate intracellular parasites of the eukaryotic cytoplasm. Pathogenic\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      species are exquisitely evolved to only proliferate within eukaryotic host cells, particularly within endothelial cells of the mammalian vasculature. Through evolution in this very specific niche,\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      have developed an inextricable dependence on multiple host functions. This absolute dependence on host cell biology offers a potential strategy for antibacterial development called host-targeted therapeutics. A previous screen of compounds that specifically target mammalian cell biology indicated that host-targeted calcium channel blockers (CCBs) inhibit\n                      <jats:italic toggle=\"yes\">Rickettsia conorii<\/jats:italic>\n                      proliferation within human cells. CCBs are routinely prescribed to human patients as antihypertensives or antianginals that function by disrupting the calcium ion equilibrium in vesicula\/cardiac smooth muscle cells. To further investigate the potential anti-\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      activities of CCBs, we sought to define the interaction between pathogenic\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      and the host Ca\n                      <jats:sup>2+<\/jats:sup>\n                      system. Achieved data demonstrate that CCBs inhibit\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      proliferation within endothelial cells, and that physical disruption of the host Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ion gradient also disrupts\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      growth. Additional analyses reveal that\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      infection leads to a rapid and persistent disruption of the host Ca\n                      <jats:sup>2+<\/jats:sup>\n                      equilibrium. By querying\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      pathogenesis, we demonstrate that some CCBs marginally disrupt rickettsial adherence to the host cell or induce apoptosis. However, all tested CCBs universally and significantly disrupt the ability of\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      to polymerize actin. Together, these data demonstrate that CCBs possess anti-\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      properties that function by disrupting rickettsial actin polymerization, and these results highlight the complex interdependence of\n                      <jats:italic toggle=\"yes\">Rickettsia<\/jats:italic>\n                      and host cell biology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00363-25","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T14:21:41Z","timestamp":1755786101000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The host calcium system contributes to intracellular\n                    <i>Rickettsia<\/i>\n                    pathogenesis"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7810-5393","authenticated-orcid":false,"given":"Jinyi C.","family":"Zhu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047s2c258","id-type":"ROR","asserted-by":"publisher"}],"name":"Biological Sciences Training Program, University of Maryland College Park","place":["College Park, USA"]},{"id":[{"id":"https:\/\/ror.org\/047s2c258","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Medicine, University of Maryland College Park","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack H.","family":"Cook","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047s2c258","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Medicine, University of Maryland College Park","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustapha","family":"Dahmani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047s2c258","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Medicine, University of Maryland College Park","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4384-4540","authenticated-orcid":true,"given":"Sean P.","family":"Riley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/047s2c258","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Medicine, University of Maryland College Park","place":["College Park, USA"]},{"name":"Virginia-Maryland College of Veterinary Medicine","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"127","article-title":"The biology of rickettsiae","volume":"5","author":"Hackstadt T","year":"1996","unstructured":"Hackstadt T. 1996. 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