{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:04:35Z","timestamp":1778850275858,"version":"3.51.4"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["0411\u201320200066"],"award-info":[{"award-number":["0411\u201320200066"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Autotransporter proteins are widely present in Gram-negative bacteria. They play a pivotal role in processes related to bacterial pathogenesis, including adhesion, invasion, colonization, biofilm formation, and cellular toxicity. Bioinformatics analysis revealed that <jats:italic>Orientia tsutsugamushi<\/jats:italic>, the causative agent of scrub typhus, encodes six different autotransporter genes (<jats:italic>scaA<\/jats:italic>\u2013<jats:italic>scaF<\/jats:italic>). Although four of these genes (<jats:italic>scaA<\/jats:italic>, <jats:italic>scaC<\/jats:italic>, <jats:italic>scaD<\/jats:italic>, and <jats:italic>scaE<\/jats:italic>) are present in diverse strains, <jats:italic>scaB<\/jats:italic> and <jats:italic>scaF<\/jats:italic> have been detected in only a limited number of strains. Previous studies have demonstrated that ScaA and ScaC are involved in the adherence of host cells. However, the putative function of other <jats:italic>O. tsutsugamushi<\/jats:italic> Sca proteins has not been studied yet. In this study, we show that <jats:italic>scaB<\/jats:italic> is transcribed and expressed on the surface of <jats:italic>O. tsutsugamushi<\/jats:italic> Boryong strain. Using a heterologous <jats:italic>Escherichia coli<\/jats:italic> expression system, we demonstrated that ScaB-expressing <jats:italic>E. coli<\/jats:italic> can successfully mediate adherence to and invasion into non-phagocytic cells, including epithelial and endothelial cells. In addition, pretreatment with a recombinant ScaB polypeptide inhibits the entry of <jats:italic>O. tsutsugamushi<\/jats:italic> into cultured mammalian cells. Finally, we also identified the <jats:italic>scaB<\/jats:italic> gene in the Kuroki and TA686 strains and observed high levels of sequence variation in the passenger domains. Here, we propose that the ScaB protein of <jats:italic>O. tsutsugamushi<\/jats:italic> can mediate both adhesion to and invasion into host cells in the absence of other <jats:italic>O. tsutsugamushi<\/jats:italic> genes and may play important roles in bacterial pathogenesis.<\/jats:p>","DOI":"10.3389\/fmicb.2021.626298","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T06:42:59Z","timestamp":1612420979000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["The Orientia tsutsugamushi ScaB Autotransporter Protein Is Required for Adhesion and Invasion of Mammalian Cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Yen Thi Hai","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaewon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyeongseok","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-il","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na-Young","family":"Ha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam-Hyuk","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"5769","DOI":"10.1128\/JB.01264-12","article-title":"Functional heterogeneity of the UpaH autotransporter protein from uropathogenic Escherichia coli","volume":"194","author":"Allsopp","year":"2012","journal-title":"J. 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Evol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"W402","DOI":"10.1093\/nar\/gkz297","article-title":"The PSIPRED protein analysis workbench: 20 years on","volume":"47","author":"Buchan","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"W349","DOI":"10.1093\/nar\/gkt381","article-title":"Scalable web services for the PSIPRED protein analysis workbench","volume":"41","author":"Buchan","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1471-2105-4-29","article-title":"MatGAT: an application that generates similarity\/identity matrices using protein or DNA sequences","volume":"4","author":"Campanella","year":"2003","journal-title":"BMC Bioinformatics"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1111\/j.1365-2958.2004.04423.x","article-title":"Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells","volume":"55","author":"Capecchi","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5272","DOI":"10.1128\/IAI.00201-09","article-title":"The Sca2 autotransporter protein from Rickettsia conorii is sufficient to mediate adherence to and invasion of cultured mammalian cells","volume":"77","author":"Cardwell","year":"2009","journal-title":"Infect. Immun."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1111\/j.1462-5822.2012.01815.x","article-title":"Identification and characterization of the mammalian association and actin-nucleating domains in the Rickettsia conorii autotransporter protein, Sca2","volume":"14","author":"Cardwell","year":"2012","journal-title":"Cell. Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1111\/j.1462-5822.2008.01279.x","article-title":"Rickettsial outer-membrane protein B (rOmpB) mediates bacterial invasion through Ku70 in an actin, c-Cbl, clathrin and caveolin 2-dependent manner","volume":"11","author":"Chan","year":"2009","journal-title":"Cell. Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"73","DOI":"10.4161\/hv.3.3.4009","article-title":"Scrub typhus vaccines: past history and recent developments","volume":"3","author":"Chattopadhyay","year":"2007","journal-title":"Hum. Vaccin."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1002\/pmic.200900633","article-title":"Global gene expression profile of Orientia tsutsugamushi","volume":"10","author":"Cho","year":"","journal-title":"Proteomics"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1128\/IAI.01316-09","article-title":"Intracellular invasion by Orientia tsutsugamushi is mediated by integrin signaling and actin cytoskeleton rearrangements","volume":"78","author":"Cho","year":"","journal-title":"Infect. Immun."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"7981","DOI":"10.1073\/pnas.0611553104","article-title":"The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host-cell interaction genes","volume":"104","author":"Cho","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s13071-015-0784-7","article-title":"Detection of Orientia sp. DNA in rodents from Asia, West Africa and Europe","volume":"8","author":"Cosson","year":"2015","journal-title":"Parasit. Vectors"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1086\/516990","article-title":"A case of scrub typhus probably acquired in Africa","volume":"25","author":"Ghorbani","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1128\/IAI.01239-10","article-title":"An autotransporter protein from Orientia tsutsugamushi mediates adherence to nonphagocytic host cells","volume":"79","author":"Ha","year":"2011","journal-title":"Infect. 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Dis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"3375","DOI":"10.1073\/pnas.0507749103","article-title":"Identification of a domain in Yersinia virulence factor YadA that is crucial for extracellular matrix-specific cell adhesion and uptake","volume":"103","author":"Heise","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1128\/IAI.69.3.1231-1243.2001","article-title":"Virulence functions of autotransporter proteins","volume":"69","author":"Henderson","year":"2001","journal-title":"Infect. Immun."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"4404","DOI":"10.1128\/JCM.01526-10","article-title":"Isolation of a novel Orientia species (O. chuto sp. nov.) from a patient infected in Dubai","volume":"48","author":"Izzard","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/tropicalmed3010011","article-title":"Scrub typhus: no longer restricted to the tsutsugamushi triangle","volume":"3","author":"Jiang","year":"2018","journal-title":"Trop. Med. Infect. Dis."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1007\/s13205-020-02389-w","article-title":"Diagnosis of scrub typhus: recent advancements and challenges","volume":"10","author":"Kala","year":"2020","journal-title":"3 Biotech"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e0004161","DOI":"10.1371\/journal.pntd.0004161","article-title":"A spatiotemporal database to track human scrub typhus using the vectormap application","volume":"9","author":"Kelly","year":"2015","journal-title":"PLoS Negl. Trop. 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Dis."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1128\/JVI.73.1.152-160.1999","article-title":"Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination","volume":"73","author":"Lole","year":"1999","journal-title":"J. Virol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e01124","DOI":"10.1128\/JCM.01124-18","article-title":"Identification and characterization of Orientia chuto in trombiculid chigger mites collected from wild rodents in Kenya","volume":"56","author":"Masakhwe","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.3389\/fmicb.2019.01163","article-title":"Type V secretion systems: an overview of passenger domain functions","volume":"10","author":"Meuskens","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/dnares\/dsn011","article-title":"The whole-genome sequencing of the obligate intracellular bacterium Orientia tsutsugamushi revealed massive gene amplification during reductive genome evolution","volume":"15","author":"Nakayama","year":"2008","journal-title":"DNA Res."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1007\/s00109-010-0600-y","article-title":"Autotransporter passenger proteins: virulence factors with common structural themes","volume":"88","author":"Nishimura","year":"2010","journal-title":"J. Mol. Med."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.cell.2006.02.012","article-title":"Bacterial adhesion and entry into host cells","volume":"124","author":"Pizarro-Cerda","year":"2006","journal-title":"Cell"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e0208327","DOI":"10.1371\/journal.pone.0208327","article-title":"Bacterial microbiome of the chigger mite Leptotrombidium imphalum varies by life stage and infection with the scrub typhus pathogen Orientia tsutsugamushi","volume":"13","author":"Ponnusamy","year":"2018","journal-title":"PLoS One"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3390\/tropicalmed5020049","article-title":"Scrub typhus: historic perspective and current status of the worldwide presence of Orientia species","volume":"5","author":"Richards","year":"2020","journal-title":"Trop. Med. Infect. Dis."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1128\/IAI.01165-09","article-title":"The Rickettsia conorii autotransporter protein Sca1 promotes adherence to nonphagocytic mammalian cells","volume":"78","author":"Riley","year":"2010","journal-title":"Infect. Immun."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S1286-4579(00)01352-6","article-title":"Orientia tsutsugamushi infection: overview and immune responses","volume":"3","author":"Seong","year":"2001","journal-title":"Microbes Infect."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"W244","DOI":"10.1093\/nar\/gki408","article-title":"The HHpred interactive server for protein homology detection and structure prediction","volume":"33","author":"S\u00f6ding","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1093\/molbev\/mst197","article-title":"MEGA6: molecular evolutionary genetics analysis version 6.0","volume":"30","author":"Tamura","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e0003971","DOI":"10.1371\/journal.pntd.0003971","article-title":"A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi)","volume":"9","author":"Taylor","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3389\/fcimb.2012.00170","article-title":"Approaches to vaccines against Orientia tsutsugamushi","volume":"2","author":"Valbuena","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1056\/NEJMoa1603657","article-title":"Endemic scrub typhus in South America","volume":"375","author":"Weitzel","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER server: new development for protein structure and function predictions","volume":"43","author":"Yang","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.626298\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T06:43:01Z","timestamp":1612420981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.626298\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":47,"alternative-id":["10.3389\/fmicb.2021.626298"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.626298","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,4]]},"article-number":"626298"}}