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Although the ultrastructure of the actin tail and host proteins associated with it are distinct from those of<jats:italic>Listeria<\/jats:italic>or<jats:italic>Shigella<\/jats:italic>, comparatively little is known regarding the rickettsial proteins involved in its organization. Here, we have used random transposon mutagenesis of<jats:italic>R. rickettsii<\/jats:italic>to generate a small-plaque mutant that is defective in actin-based motility and does not spread directly from cell to cell as is characteristic of spotted fever group rickettsiae. The transposon insertion site of this mutant strain was within Sca2, a member of a family of large autotransporter proteins. Sca2 exhibits several features suggestive of its apparent role in actin-based motility. It displays an N-terminal secretory signal peptide, a C-terminal predicted autotransporter domain, up to four predicted Wasp homology 2 (WH2) domains, and two proline-rich domains, one with similarity to eukaryotic formins. In a guinea pig model of infection, the Sca2 mutant did not elicit fever, suggesting that Sca2 and actin-based motility are virulence factors of spotted fever group rickettsiae.<\/jats:p>","DOI":"10.1128\/iai.00100-10","type":"journal-article","created":{"date-parts":[[2010,3,2]],"date-time":"2010-03-02T04:34:14Z","timestamp":1267504454000},"page":"2240-2247","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":150,"title":["Disruption of the<i>Rickettsia rickettsii<\/i>Sca2 Autotransporter Inhibits Actin-Based Motility"],"prefix":"10.1128","volume":"78","author":[{"given":"Betsy","family":"Kleba","sequence":"first","affiliation":[{"name":"Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina R.","family":"Clark","sequence":"additional","affiliation":[{"name":"Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika I.","family":"Lutter","sequence":"additional","affiliation":[{"name":"Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damon W.","family":"Ellison","sequence":"additional","affiliation":[{"name":"Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Hackstadt","sequence":"additional","affiliation":[{"name":"Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.25.1.167-171.1987"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.27.2.468-474.1980"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.3.825-827.1987"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.44.3.559-564.1984"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0402.980205"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.11.6628-6636.2004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002582"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"770","DOI":"10.4049\/jimmunol.90.5.770","volume":"90","year":"1963","unstructured":"Bell, E. 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