{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:34:04Z","timestamp":1791120844653,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107-2314-B-002-279-MY2"],"award-info":[{"award-number":["MOST 107-2314-B-002-279-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOHW113-CDC-C-315-144315"],"award-info":[{"award-number":["MOHW113-CDC-C-315-144315"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taiwan CDC","award":["MOST 107-2314-B-002-279-MY2"],"award-info":[{"award-number":["MOST 107-2314-B-002-279-MY2"]}]},{"name":"Taiwan CDC","award":["MOHW113-CDC-C-315-144315"],"award-info":[{"award-number":["MOHW113-CDC-C-315-144315"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Orientia tsutsugamushi is an obligate intracellular bacterium associated with trombiculid mites and is the causative agent of scrub typhus, a life-threatening febrile disease. Strain typing of O. tsutsugamushi is based on its immunodominant surface antigen, 56-kDa type-specific antigen (TSA56). However, TSA56 gene sequence-based phylogenetic analysis is only partially congruent with core genome-based phylogenetic analysis. Thus, this study investigated whether concatenated surface antigen sequences, including surface cell antigen (Sca) proteins, can reflect the genome-scale phylogeny of O. tsutsugamushi. Complete genomes were obtained for two common O. tsutsugamushi strains in Taiwan, TW-1 and TW-22, and the core genome\/proteome was identified for 11 O. tsutsugamushi strains. Phylogenetic analysis was performed using maximum likelihood (ML) and neighbor-joining (NJ) methods, and the congruence between trees was assessed using a quartet similarity measure. Phylogenetic analysis based on 691 concatenated core protein sequences produced identical tree topologies with ML and NJ methods. Among TSA56 and core Sca proteins (ScaA, ScaC, ScaD, and ScaE), TSA56 trees were most similar to the core protein tree, and ScaA trees were the least similar. However, concatenated ScaA and TSA56 sequences produced trees that were highly similar to the core protein tree, the NJ tree being more similar. Strain-level characterization of O. tsutsugamushi may be improved by coanalyzing ScaA and TSA56 sequences, which are also important targets for their combined immunogenicity.<\/jats:p>","DOI":"10.3390\/pathogens13040299","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:58:38Z","timestamp":1712105918000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Concatenated ScaA and TSA56 Surface Antigen Sequences Reflect Genome-Scale Phylogeny of Orientia tsutsugamushi: An Analysis Including Two Genomes from Taiwan"],"prefix":"10.3390","volume":"13","author":[{"given":"Nicholas T.","family":"Minahan","sequence":"first","affiliation":[{"name":"Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei 100025, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Ying","family":"Yen","sequence":"additional","affiliation":[{"name":"Centers for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei 115210, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-4809","authenticated-orcid":false,"given":"Yue-Liang Leon","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei 100025, Taiwan"},{"name":"Department of Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Taipei 100025, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yun","family":"Shu","sequence":"additional","affiliation":[{"name":"Centers for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei 115210, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6154-113X","authenticated-orcid":false,"given":"Kun-Hsien","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei 100025, Taiwan"},{"name":"Global Health Program, College of Public Health, National Taiwan University, Taipei 100025, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","first-page":"219","article-title":"Ecological considerations in scrub typhus. 2. Vector species","volume":"39","author":"Traub","year":"1968","journal-title":"Bull. World Health Organ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.4269\/ajtmh.13-0064","article-title":"Unresolved problems related to scrub typhus: A seriously neglected life-threatening disease","volume":"89","author":"Paris","year":"2013","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jiang, J., and Richards, A.L. (2018). Scrub typhus: No longer restricted to the Tsutsugamushi Triangle. Trop. Med. Infect. Dis., 3.","DOI":"10.3390\/tropicalmed3010011"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Minahan, N.T., Chao, C.C., and Tsai, K.H. (2018). The re-emergence and emergence of vector-borne rickettsioses in Taiwan. Trop. Med. Infect. Dis., 3.","DOI":"10.3390\/tropicalmed3010001"},{"key":"ref_5","first-page":"CD002150","article-title":"Antibiotics for treating scrub typhus","volume":"9","author":"Liu","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.jfma.2019.08.036","article-title":"Australian case of scrub typhus contracted while hiking in northern Taiwan","volume":"119","author":"Minahan","year":"2020","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Devasagayam, E., Dayanand, D., Kundu, D., Kamath, M.S., Kirubakaran, R., and Varghese, G.M. (2021). The burden of scrub typhus in India: A systematic review. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009619"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bonell, A., Lubell, Y., Newton, P.N., Crump, J.A., and Paris, D.H. (2017). Estimating the burden of scrub typhus: A systematic review. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005838"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Valbuena, G., and Walker, D.H. (2012). Approaches to vaccines against Orientia tsutsugamushi. Front. Cell Infect. Microbiol., 2.","DOI":"10.3389\/fcimb.2012.00170"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1128\/iai.58.7.2076-2084.1990","article-title":"The 56-kilodalton major protein antigen of Rickettsia tsutsugamushi: Molecular cloning and sequence analysis of the sta56 gene and precise identification of a strain-specific epitope","volume":"58","author":"Stover","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","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":"2010","journal-title":"Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1084\/jem.87.4.339","article-title":"Studies on scrub typhus (tsutsugamushi disease). III. Heterogenicity of strains of R. tsutsugamushi as demonstrated by cross-vaccination studies","volume":"87","author":"Rights","year":"1948","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"568","DOI":"10.3181\/00379727-112-28107","article-title":"Serological diagnosis of scrub typhus by indirect immunofluorescence","volume":"112","author":"Bozeman","year":"1963","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1086\/510585","article-title":"Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: A lack of consensus leads to a lot of confusion","volume":"44","author":"Blacksell","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kelly, D.J., Fuerst, P.A., and Richards, A.L. (2019). Origins, importance and genetic stability of the prototype strains Gilliam, Karp and Kato of Orientia tsutsugamushi. Trop. Med. Infect. Dis., 4.","DOI":"10.3390\/tropicalmed4020075"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1348-0421.1986.tb02987.x","article-title":"Production and characterization of monoclonal strain-specific antibodies against prototype strains of Rickettsia tsutsugamushi","volume":"30","author":"Murata","year":"1986","journal-title":"Microbiol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/j.1348-0421.1986.tb02988.x","article-title":"Immunological properties of Rickettsia tsutsugamushi, Kawasaki strain, isolated from a patient in Kyushu","volume":"30","author":"Yamamoto","year":"1986","journal-title":"Microbiol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1128\/jcm.28.9.2111-2113.1990","article-title":"Characterization of a new antigenic type, Kuroki, of Rickettsia tsutsugamushi isolated from a patient in Japan","volume":"28","author":"Ohashi","year":"1990","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1128\/jcm.28.4.685-688.1990","article-title":"Serological classification by monoclonal antibodies of Rickettsia tsutsugamushi isolated in Korea","volume":"28","author":"Chang","year":"1990","journal-title":"J. Clin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/j.1348-0421.1996.tb01120.x","article-title":"Demonstration of antigenic and genotypic variation in Orientia tsutsugamushi which were isolated in Japan, and their classification into type and subtype","volume":"40","author":"Ohashi","year":"1996","journal-title":"Microbiol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1574-6968.1999.tb08791.x","article-title":"Phylogenetic analysis of Orientia tsutsugamushi strains based on the sequence homologies of 56-kDa type-specific antigen genes","volume":"180","author":"Enatsu","year":"1999","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1574-695X.2007.00375.x","article-title":"Genetic typing of the 56-kDa type-specific antigen gene of contemporary Orientia tsutsugamushi isolates causing human scrub typhus at two sites in north-eastern and western Thailand","volume":"52","author":"Blacksell","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"658","DOI":"10.4269\/ajtmh.2010.09-0608","article-title":"Phylogenetic analysis of 56-kDa type-specific antigen gene of Orientia tsutsugamushi isolates in Taiwan","volume":"83","author":"Lu","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1128\/AEM.02796-10","article-title":"Genetic typing, based on the 56-kilodalton type-specific antigen gene, of Orientia tsutsugamushi strains isolated from chiggers collected from wild-caught rodents in Taiwan","volume":"77","author":"Lin","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chen, H.F., Peng, S.H., Tsai, K.H., Yang, C.F., Chang, M.C., Hsueh, Y.L., Su, C.L., Wang, R.Y., Shu, P.Y., and Yang, S.L. (2022). Molecular epidemiology of scrub typhus in Taiwan during 2006\u20132016. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0011025"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.3201\/eid1210.051697","article-title":"Scrub typhus in Himalayas","volume":"12","author":"Mahajan","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Trung, N.V., Hoi, L.T., Cuong, D.D., Ha, D.T., Hoa, T.M., Lien, V.N., Hoa, N.T., Hoa, L.N.M., Huong, D.T., and Bich, V.T.N. (2019). Analysis of the 56-kDa type specific antigen gene of Orientia tsutsugamushi from northern Vietnam. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221588"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kim, G., Ha, N.Y., Min, C.K., Kim, H.I., Yen, N.T.H., Lee, K.H., Oh, I., Kang, J.S., Choi, M.S., and Kim, I.S. (2017). Diversification of Orientia tsutsugamushi genotypes by intragenic recombination and their potential expansion in endemic areas. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005408"},{"key":"ref_29","doi-asserted-by":"crossref","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. USA"},{"key":"ref_30","doi-asserted-by":"crossref","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":"ref_31","doi-asserted-by":"crossref","unstructured":"Batty, E.M., Chaemchuen, S., Blacksell, S., Richards, A.L., Paris, D., Bowden, R., Chan, C., Lachumanan, R., Day, N., and Donnelly, P. (2018). Long-read whole genome sequencing and comparative analysis of six strains of the human pathogen Orientia tsutsugamushi. PLoS Negl. Trop. Dis., 12.","DOI":"10.1101\/280958"},{"key":"ref_32","first-page":"e000199","article-title":"Comparative pan-genomic analyses of Orientia tsutsugamushi reveal an exceptional model of bacterial evolution driving genomic diversity","volume":"4","author":"Fleshman","year":"2018","journal-title":"Microb. Genom."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D851","DOI":"10.1093\/nar\/gkx1068","article-title":"RefSeq: An update on prokaryotic genome annotation and curation","volume":"46","author":"Haft","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00268-23","DOI":"10.1128\/msphere.00268-23","article-title":"Orientia tsutsugamushi: Comprehensive analysis of the mobilome of a highly fragmented and repetitive genome reveals the capacity for ongoing lateral gene transfer in an obligate intracellular bacterium","volume":"8","author":"Giengkam","year":"2023","journal-title":"mSphere"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1574-6968.1995.tb07372.x","article-title":"Phylogenetic position of Rickettsia tsutsugamushi and the relationship among its antigenic variants by analyses of 16S rRNA gene sequences","volume":"125","author":"Ohashi","year":"1995","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1099\/00207713-45-3-589","article-title":"Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov","volume":"45","author":"Tamura","year":"1995","journal-title":"Int. J. Syst. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gillespie, J.J., and Salje, J. (2023). Orientia and Rickettsia: Different flowers from the same garden. Curr. Opin. Microbiol., 74.","DOI":"10.1016\/j.mib.2023.102318"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/1040841X.2013.804032","article-title":"Autotransporter-based cell surface display in Gram-negative bacteria","volume":"41","author":"Nicolay","year":"2015","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1099\/ijsem.0.003963","article-title":"Genome sequence-based criteria for demarcation and definition of species in the genus Rickettsia","volume":"70","author":"Diop","year":"2020","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1128\/JCM.41.12.5456-5465.2003","article-title":"Gene sequence-based criteria for identification of new Rickettsia isolates and description of Rickettsia heilongjiangensis sp. nov","volume":"41","author":"Fournier","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Koralur, M.C., Ramaiah, A., and Dasch, G.A. (2018). Detection and distribution of Sca autotransporter protein antigens in diverse isolates of Orientia tsutsugamushi. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006784"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nguyen, Y.T.H., Kim, C., Kim, H.I., Kim, Y., Lee, S.E., Chang, S., Ha, N.Y., and Cho, N.H. (2023). An alternative splicing variant of the Mixed-Lineage Leukemia 5 protein is a cellular adhesion receptor for ScaA of Orientia tsutsugamushi. mBio, 14.","DOI":"10.1128\/mbio.01543-22"},{"key":"ref_43","doi-asserted-by":"crossref","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. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ha, N.Y., Sharma, P., Kim, G., Kim, Y., Min, C.K., Choi, M.S., Kim, I.S., and Cho, N.H. (2015). Immunization with an autotransporter protein of Orientia tsutsugamushi provides protective immunity against scrub typhus. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003585"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Giengkam, S., Blakes, A., Utsahajit, P., Chaemchuen, S., Atwal, S., Blacksell, S.D., Paris, D.H., Day, N.P.J., and Salje, J. (2015). Improved quantification, propagation, purification and storage of the obligate intracellular human pathogen Orientia tsutsugamushi. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004009"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sunyakumthorn, P., Paris, D.H., Chan, T.C., Jones, M., Luce-Fedrow, A., Chattopadhyay, S., Jiang, J., Anantatat, T., Turner, G.D.H., and Day, N.P.J. (2013). An intradermal inoculation model of scrub typhus in Swiss CD-1 mice demonstrates more rapid dissemination of virulent strains of Orientia tsutsugamushi. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054570"},{"key":"ref_47","unstructured":"Kassambara, A. (2023, April 25). ggpubr: \u2018ggplot2\u2019 Based Publication Ready Plots. Available online: https:\/\/cran.r-project.org\/web\/packages\/ggpubr\/index.html."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/s41587-019-0217-9","article-title":"Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome","volume":"37","author":"Wenger","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: Pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1093\/bioinformatics\/btp450","article-title":"ShortRead: A bioconductor package for input, quality assessment and exploration of high-throughput sequence data","volume":"25","author":"Morgan","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_52","first-page":"10","article-title":"Biostrings: Efficient manipulation of biological strings","volume":"2","author":"Aboyoun","year":"2023","journal-title":"R Package Version"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41592-020-01056-5","article-title":"Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm","volume":"18","author":"Cheng","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hunt, M., Silva, N.D., Otto, T.D., Parkhill, J., Keane, J.A., and Harris, S.R. (2015). Circlator: Automated circularization of genome assemblies using long sequencing reads. Genome Biol., 16.","DOI":"10.1186\/s13059-015-0849-0"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1101\/gr.215087.116","article-title":"Canu: Scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation","volume":"27","author":"Koren","year":"2017","journal-title":"Genome Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows\u2013Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Walker, B.J., Abeel, T., Shea, T., Priest, M., Abouelliel, A., Sakthikumar, S., Cuomo, C.A., Zeng, Q., Wortman, J., and Young, S.K. (2014). Pilon: An integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112963"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6614","DOI":"10.1093\/nar\/gkw569","article-title":"NCBI prokaryotic genome annotation pipeline","volume":"44","author":"Tatusova","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"W484","DOI":"10.1093\/nar\/gkad326","article-title":"Proksee: In-depth characterization and visualization of bacterial genomes","volume":"51","author":"Grant","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_60","first-page":"D84","article-title":"GenBank","volume":"48","author":"Sayers","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2014A multiple sequence alignment editor and analysis workbench","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W88","DOI":"10.1093\/nar\/gkz423","article-title":"M1CR0B1AL1Z3R\u2014A user-friendly web server for the analysis of large-scale microbial genomics data","volume":"47","author":"Avram","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis Version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","article-title":"trimAl: A tool for automated alignment trimming in large-scale phylogenetic analyses","volume":"25","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.1093\/bioinformatics\/btz305","article-title":"RAxML-NG: A fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference","volume":"35","author":"Kozlov","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_67","first-page":"406","article-title":"The neighbor-joining method: A new method for reconstructing phylogenetic trees","volume":"4","author":"Saitou","year":"1987","journal-title":"Mol. Biol. Evol."},{"key":"ref_68","first-page":"275","article-title":"The rapid generation of mutation data matrices from protein sequences","volume":"8","author":"Jones","year":"1992","journal-title":"Comput. Appl. Biosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"783","DOI":"10.2307\/2408678","article-title":"Confidence limits on phylogenies: An approach using the bootstrap","volume":"39","author":"Felsenstein","year":"1985","journal-title":"Evolution"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.2041-210X.2011.00169.x","article-title":"phytools: An R package for phylogenetic comparative biology (and other things)","volume":"3","author":"Revell","year":"2012","journal-title":"Methods Ecol. Evol."},{"key":"ref_71","unstructured":"Smith, M.R. (2022). Quartet: Comparison of Phylogenetic Trees Using Quartet and Split Measures, CERN."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1093\/sysbio\/syab072","article-title":"Phylogenetic signal and bias in paleontology","volume":"71","author":"Asher","year":"2022","journal-title":"Syst. Biol."},{"key":"ref_73","first-page":"47","article-title":"Secretome of obligate intracellular Rickettsia","volume":"39","author":"Gillespie","year":"2015","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1080\/22221751.2019.1632676","article-title":"Immunization with a recombinant antigen composed of conserved blocks from TSA56 provides broad genotype protection against scrub typhus","volume":"8","author":"Kim","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1128\/iai.61.5.1674-1681.1993","article-title":"Murine T-cell response to native and recombinant protein antigens of Rickettsia tsutsugamushi","volume":"61","author":"Hickman","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S0264-410X(00)00167-5","article-title":"Neutralization epitopes on the antigenic domain II of the Orientia tsutsugamushi 56-kDa protein revealed by monoclonal antibodies","volume":"19","author":"Seong","year":"2000","journal-title":"Vaccine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"532","DOI":"10.4269\/ajtmh.18-0391","article-title":"Evaluation of enzyme-linked immunosorbent assay using recombinant 56-kDa type-specific antigens derived from multiple Orientia tsutsugamushi strains for detection of scrub typhus infection","volume":"100","author":"Yang","year":"2019","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1128\/CVI.00017-11","article-title":"Kinetics and magnitude of antibody responses against the conserved 47-kilodalton antigen and the variable 56-kilodalton antigen in scrub typhus patients","volume":"18","author":"Chen","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1128\/CVI.00553-15","article-title":"Diagnostic accuracy of the InBios scrub typhus detect enzyme-linked immunoassay for the detection of IgM antibodies in northern Thailand","volume":"23","author":"Blacksell","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e116","DOI":"10.1038\/emi.2017.106","article-title":"Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients","volume":"6","author":"Ha","year":"2017","journal-title":"Emerg. Microbes Infect."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0882-4010(91)90090-W","article-title":"Molecular cloning and sequence analysis of a Rickettsia tsutsugamushi 22 kDa antigen containing B- and T-cell epitopes","volume":"11","author":"Hickman","year":"1991","journal-title":"Microb. Pathog."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.micpath.2013.06.002","article-title":"Involvement of lipid rafts in the budding-like exit of Orientia tsutsugamushi","volume":"63","author":"Kim","year":"2013","journal-title":"Microb. Pathog."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.4110\/in.2023.23.e47","article-title":"Intranasal immunization with nanoparticles containing an Orientia tsutsugamushi protein vaccine candidate and a polysorbitol transporter adjuvant enhances both humoral and cellular immune responses","volume":"23","author":"Kim","year":"2023","journal-title":"Immune Netw."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Park, J., Zhang, Z., Belinskaya, T., Tsoras, A.N., Chao, C.C., Jiang, L., and Champion, J.A. (2023). Dual-antigen subunit vaccine nanoparticles for scrub typhus. Pathogens, 12.","DOI":"10.3390\/pathogens12121390"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41586-021-03365-x","article-title":"Quadrivalent influenza nanoparticle vaccines induce broad protection","volume":"592","author":"Ellis","year":"2021","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Nguyen, Y.T.H., Kim, C., Kim, Y., Jeon, K., Kim, H.I., Ha, N.Y., and Cho, N.H. (2021). The Orientia tsutsugamushi ScaB autotransporter protein is required for adhesion and invasion of mammalian cells. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.626298"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1038\/s41467-020-17094-8","article-title":"Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen","volume":"11","author":"Giengkam","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Paris, D.H., Phetsouvanh, R., Tanganuchitcharnchai, A., Jones, M., Jenjaroen, K., Vongsouvath, M., Ferguson, D.P.J., Blacksell, S.D., Newton, P.N., and Day, N.P.J. (2012). Orientia tsutsugamushi in human scrub typhus eschars shows tropism for dendritic cells and monocytes rather than endothelium. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001466"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Inthawong, M., Sunyakumthorn, P., Wongwairot, S., Anantatat, T., Dunachie, S.J., Im-Erbsin, R., Jones, J.W., Mason, C.J., Lugo, L.A., and Blacksell, S.D. (2022). A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010611"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"816","DOI":"10.3389\/fimmu.2018.00816","article-title":"Dissemination of Orientia tsutsugamushi, a causative agent of scrub typhus, and immunological responses in the humanized DRAGA mouse","volume":"9","author":"Jiang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_91","first-page":"213","article-title":"Life-threatening scrub typhus with meningoencephalitis and acute respiratory distress syndrome","volume":"96","author":"Fang","year":"1997","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_92","first-page":"385","article-title":"Clinical manifestations and complications of rickettsiosis in southern Taiwan","volume":"101","author":"Lee","year":"2002","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Fisher, J., Gonzales, C., Chroust, Z., Liang, Y., and Soong, L. (2023). Orientia tsutsugamushi infection stimulates Syk-dependent responses and innate cytosolic defenses in macrophages. Pathogens, 12.","DOI":"10.20944\/preprints202211.0331.v1"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/jmedent\/11.3.237","article-title":"The ecology of chigger-borne rickettsiosis (scrub typhus)","volume":"11","author":"Traub","year":"1974","journal-title":"J. Med. Entomol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1186\/s13071-017-2535-4","article-title":"Tick-borne pathogens in ticks collected from birds in Taiwan","volume":"10","author":"Kuo","year":"2017","journal-title":"Parasit. Vectors"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/jme\/tjv139","article-title":"A checklist of chigger mites (Acari: Trombiculidae and Leeuwenh\u00f6kiidae) from Taiwan, with descriptions of three new species","volume":"52","author":"Chung","year":"2015","journal-title":"J. Med. Entomol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1089\/vbz.2014.1753","article-title":"Transovarial transmission of co-existing Orientia tsutsugamushi genotypes in laboratory-reared Leptotrombidium imphalum","volume":"16","author":"Takhampunya","year":"2016","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jmii.2022.12.006","article-title":"Rickettsia felis is an emerging human pathogen associated with cat fleas: A review of findings in Taiwan","volume":"56","author":"Minahan","year":"2023","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_99","doi-asserted-by":"crossref","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":"ref_100","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.3201\/eid2609.200918","article-title":"Molecular description of a novel Orientia species causing scrub typhus in South America","volume":"26","author":"Abarca","year":"2020","journal-title":"Emerg. Infect. Dis."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/4\/299\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:22:43Z","timestamp":1760106163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/4\/299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":100,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["pathogens13040299"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13040299","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]}}}