{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:55:43Z","timestamp":1787644543502,"version":"build-2736575974"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01 AI109044"],"award-info":[{"award-number":["R01 AI109044"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,2,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic>Rickettsia parkeri<\/jats:italic>\n                      is an obligate intracellular, tick-borne bacterial pathogen that can cause eschar-associated rickettsiosis in humans.\n                      <jats:italic>R. parkeri<\/jats:italic>\n                      invades host cells, escapes from vacuoles into the cytosol, and undergoes two independent modes of actin-based motility mediated by effectors RickA or Sca2. Actin-based motility of\n                      <jats:italic>R. parkeri<\/jats:italic>\n                      enables bacteria to enter protrusions of the host cell plasma membrane that are engulfed by neighboring host cells. However, whether and how RickA and Sca2 independently contribute to cell-to-cell spread\n                      <jats:italic>in vitro<\/jats:italic>\n                      or pathogenicity\n                      <jats:italic>in vivo<\/jats:italic>\n                      has been unclear. Using live cell imaging of\n                      <jats:italic>rickA<\/jats:italic>\n                      ::Tn and\n                      <jats:italic>sca2<\/jats:italic>\n                      ::Tn mutants, we discovered both RickA and Sca2 contribute to different modes of cell-to-cell spread. Compared with Sca2-spread, RickA-spread involves the formation of longer protrusions that exhibit larger fluctuations in length and take a longer time to be engulfed into neighboring cells. We further compared the roles of RickA and Sca2\n                      <jats:italic>in vivo<\/jats:italic>\n                      following intradermal (i.d.) infection of\n                      <jats:italic>Ifnar1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ;\n                      <jats:italic>Ifngr1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice carrying knockout mutations in the genes encoding the receptors for IFN-I (\n                      <jats:italic>Ifnar1<\/jats:italic>\n                      ) and IFN-\u03b3 (\n                      <jats:italic>Ifngr1<\/jats:italic>\n                      ), which exhibit eschars and succumb to infection with wild-type (WT)\n                      <jats:italic>R. parkeri<\/jats:italic>\n                      . We observed that RickA is important for severe eschar formation, whereas Sca2 contributes to larger foci of infection in the skin and dissemination from the skin to the internal organs. Our results suggest that actin-based motility effectors RickA and Sca2 drive two distinct forms of cell-to-cell spread and contribute differently to pathogenicity in the mammalian host.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic>Rickettsia parkeri<\/jats:italic>\n                        , a bacterium in the spotted fever group of\n                        <jats:italic>Rickettsia<\/jats:italic>\n                        species, can be transmitted from ticks to humans, leading to symptoms including fever, rash, muscle aches, and a lesion at the site of the tick bite. During\n                        <jats:italic>Rickettsia parkeri<\/jats:italic>\n                        infection, bacteria invade cells within the animal host, proliferate in the host cell\u2019s cytosol, move using a process called actin-based motility, and spread to neighboring host cells.\n                        <jats:italic>Rickettsia parkeri<\/jats:italic>\n                        is unusual in having two bacterial proteins that mediate actin-based motility. The significance of our research is to reveal that each of these bacterial actin-based motility proteins contributes differently to spread between cells and to the signs of infection in a mouse model of spotted fever disease. Our results are important for understanding the contribution of actin-based motility to mammalian infection by\n                        <jats:italic>Rickettsia parkeri<\/jats:italic>\n                        as well as to infection by other bacterial and viral pathogens that require this process to spread between cells and cause disease.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02563-24","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T09:01:09Z","timestamp":1737104469000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["The\n                    <i>Rickettsia<\/i>\n                    actin-based motility effectors RickA and Sca2 contribute differently to cell-to-cell spread and pathogenicity"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5109-7362","authenticated-orcid":false,"given":"Cuong J.","family":"Tran","sequence":"first","affiliation":[{"name":"Division of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley","place":["Berkeley, USA"]},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6078-880X","authenticated-orcid":false,"given":"Zahra","family":"Zubair-Nizami","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley","place":["Berkeley, USA"]},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley","place":["Berkeley, 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