Tamura A , Ohashi N , Urakami H , Miyamura S , 1995. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Evol Microbiol 45: 589–591.
Kelly DJ , Fuerst PA , Ching WM , Richards AL , 2009. Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin Infect Dis 48 (Suppl 3 ):S203–S230.
Weitzel T , Dittrich S , Lopez J , Phuklia W , Martinez-Valdebenito C , Velasquez K , Blacksell SD , Paris DH , Abarca K , 2016. Endemic scrub typhus in South America. N Engl J Med 375: 954–961.
Taylor AJ , Paris DH , Newton PN , 2015. A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi). PLoS Negl Trop Dis 9: e0003971.
Sonthayanon P , Chierakul W , Wuthiekanun V , Phimda K , Pukrittayakamee S , Day NP , Peacock SJ , 2009. Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus. J Clin Microbiol 47: 430–434.
Ge H , Tong M , Li A , Mehta R , Ching WM , 2005. Cloning and sequence analysis of the 22-kDa antigen genes of Orientia tsutsugamushi strains Kato, TA763, AFSC 7, 18-032460, TH1814, and MAK 119. Ann N Y Acad Sci 1063: 231–238.
Niu D , Chen W , Zhang X , Chen M , Cui H , Wei W , Wen B , Chen X , 2003. Immunogenicity of a 40kDa fragment of the 47kDa recombinant protein and DNA vaccine from Karp strain of Orientia tsutsugamushi. Ann N Y Acad Sci 990: 527–534.
Qiang Y , Tamura A , Urakami H , Makisaka Y , Koyama S , Fukuhara M , Kadosaka T , 2003. Phylogenetic characterization of Orientia tsutsugamushi isolated in Taiwan according to the sequence homologies of 56-kDa type-specific antigen genes. Microbiol Immunol 47: 577–583.
Sonthayanon P , Peacock SJ , Chierakul W , Wuthiekanun V , Blacksell SD , Holden MT , Bentley SD , Feil EJ , Day NP , 2010. High rates of homologous recombination in the mite endosymbiont and opportunistic human pathogen Orientia tsutsugamushi. PLoS Negl Trop Dis 4: e752.
Duong V , Blassdell K , May TT , Sreyrath L , Gavotte L , Morand S , Frutos R , Buchy P , 2013. Diversity of Orientia tsutsugamushi clinical isolates in Cambodia reveals active selection and recombination process. Infect Genet Evol 15: 25–34.
Phetsouvanh R , Sonthayanon P , Pukrittayakamee S , Paris DH , Newton PN , Feil EJ , Day NP , 2015. The diversity and geographical structure of Orientia tsutsugamushi strains from patients with scrub typhus in Laos. PLoS Negl Trop Dis 9: e0004024.
Lee YM , Kim DM , Lee SH , Jang MS , Neupane GP , 2011. Phylogenetic analysis of the 56 kDa protein genes of Orientia tsutsugamushi in southwest area of Korea. Am J Trop Med Hyg 84: 250–254.
Jolley KA , Bray JE , Maiden MCJ , 2018. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 3: 124.
Francisco AP , Bugalho M , Ramirez M , Carrico JA , 2009. Global optimal eBURST analysis of multilocus typing data using a graphic matroid approach. BMC Bioinformatics 10: 152.
Jolley KA , Feil E , Chan M-S , Maiden MCJ , 2001. Sequence type analysis and recombinational tests (START). Bioinformatics 17: 1230–1231.
Kumar S , Stecher G , Li M , Knyaz C , Tamura K , 2018. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35: 1547–1549.
Holsinger KE , Weir BS , 2009. Genetics in geographically structured populations: defining, estimating and interpreting FST . Nat Rev Genet 10: 639.
Simpson EH , 1949. Measurement of diversity. Nature 163: 688.
Grundmann H , Hori S , Tanner G , 2001. Determining confidence intervals when measuring genetic diversity and the discriminatory abilities of typing methods for microorganisms. J Clin Microbiol 39: 4190–4192.
Rozas J , Ferrer-Mata A , Sanchez-DelBarrio JC , Guirao-Rico S , Librado P , Ramos-Onsins SE , Sanchez-Gracia A , 2017. DnaSP 6: DNA sequence polymorphism analysis of large data sets. Mol Biol Evol 34: 3299–3302.
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Orientia tsutsugamushi, an obligate intracellular organism, is the causative agent of scrub typhus. Multilocus sequence typing (MLST) is a genetic typing method that provides a unified bacterial isolate characterization approach. However, there are no comparative studies in South Korea on the genotypic properties of O. tsutsugamushi based on MLST. To conduct a comparative analysis with previous data collected from Thailand, Laos, and Japan, we investigated the genetic diversity of O. tsutsugamushi from 51 patients with scrub typhus in South Korea by using MLST. The MLST analysis revealed 10 new alleles in the housekeeping genes: gpsA, n = 2; mdh, n = 1; nrdB, n = 1; nuoF, n = 1; ppdK, n = 1; sucB, n = 2; and sucD, n = 2. These novel alleles led to the assignment of six new sequence types (STs) (ST93–98). The 51 samples corresponded to seven different STs (ST48 and ST93–98), with ST48 accounting for the largest proportion (49.0%) of O. tsutsugamushi STs in South Korea. Interestingly, O. tsutsugamushi from patients with scrub typhus in South Korea were clustered in two different clades, and the five Korean STs (ST48, ST93, ST94, ST95, and ST98) were close genetically to ST80, which was isolated from Laos. The remaining two STs (ST96 and ST97) were close genetically to ST49 (Ikeda, Japan). Overall, our results suggest that the relative genetic stability and the clonal populations of O. tsutsugamushi strains in South Korea have remained mostly conserved.
These authors contributed equally to this work.
Financial support: This work is funded by the Basic Science Research Programs (NRF-2018R1D1A3B07049557 and 2019R1A6A1A11052070) of the National Research Foundation of Korea, which are funded by the Ministry of Education and the Fund of Biomedical Research Institute, Jeonbuk National University Hospital.
Disclaimer: Study funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Authors’ addresses: Joo-Hee Hwang and Chang-Seop Lee, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea, and Research Institute of Clinical Medicine of Jeonbuk National University–Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea, E-mails: zany78@naver.com and lcsmd@jbnu.ac.kr. Jeongsik Kim, Faculty of Science Education, Jeju National University, Jeju, Republic of Korea, and Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju, Republic of Korea, E-mail: yorus@jejunu.ac.kr. In O. Sun, Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Republic of Korea, E-mail: inogood77@gmail.com. Tae Hee Lee, Department of Microbiology and Immunology, Jeonbuk National University Medical School, Jeonju, Republic of Korea, and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Republic of Korea, E-mail: leeth@jbnu.ac.kr. Kyung Min Chung, Research Institute of Clinical Medicine of Jeonbuk National University–Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea, Department of Microbiology and Immunology, Jeonbuk National University Medical School, Jeonju, Republic of Korea, and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Republic of Korea, E-mail: kmin@jbnu.ac.kr.
Tamura A , Ohashi N , Urakami H , Miyamura S , 1995. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Evol Microbiol 45: 589–591.
Kelly DJ , Fuerst PA , Ching WM , Richards AL , 2009. Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi. Clin Infect Dis 48 (Suppl 3 ):S203–S230.
Weitzel T , Dittrich S , Lopez J , Phuklia W , Martinez-Valdebenito C , Velasquez K , Blacksell SD , Paris DH , Abarca K , 2016. Endemic scrub typhus in South America. N Engl J Med 375: 954–961.
Taylor AJ , Paris DH , Newton PN , 2015. A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi). PLoS Negl Trop Dis 9: e0003971.
Sonthayanon P , Chierakul W , Wuthiekanun V , Phimda K , Pukrittayakamee S , Day NP , Peacock SJ , 2009. Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus. J Clin Microbiol 47: 430–434.
Ge H , Tong M , Li A , Mehta R , Ching WM , 2005. Cloning and sequence analysis of the 22-kDa antigen genes of Orientia tsutsugamushi strains Kato, TA763, AFSC 7, 18-032460, TH1814, and MAK 119. Ann N Y Acad Sci 1063: 231–238.
Niu D , Chen W , Zhang X , Chen M , Cui H , Wei W , Wen B , Chen X , 2003. Immunogenicity of a 40kDa fragment of the 47kDa recombinant protein and DNA vaccine from Karp strain of Orientia tsutsugamushi. Ann N Y Acad Sci 990: 527–534.
Qiang Y , Tamura A , Urakami H , Makisaka Y , Koyama S , Fukuhara M , Kadosaka T , 2003. Phylogenetic characterization of Orientia tsutsugamushi isolated in Taiwan according to the sequence homologies of 56-kDa type-specific antigen genes. Microbiol Immunol 47: 577–583.
Sonthayanon P , Peacock SJ , Chierakul W , Wuthiekanun V , Blacksell SD , Holden MT , Bentley SD , Feil EJ , Day NP , 2010. High rates of homologous recombination in the mite endosymbiont and opportunistic human pathogen Orientia tsutsugamushi. PLoS Negl Trop Dis 4: e752.
Duong V , Blassdell K , May TT , Sreyrath L , Gavotte L , Morand S , Frutos R , Buchy P , 2013. Diversity of Orientia tsutsugamushi clinical isolates in Cambodia reveals active selection and recombination process. Infect Genet Evol 15: 25–34.
Phetsouvanh R , Sonthayanon P , Pukrittayakamee S , Paris DH , Newton PN , Feil EJ , Day NP , 2015. The diversity and geographical structure of Orientia tsutsugamushi strains from patients with scrub typhus in Laos. PLoS Negl Trop Dis 9: e0004024.
Lee YM , Kim DM , Lee SH , Jang MS , Neupane GP , 2011. Phylogenetic analysis of the 56 kDa protein genes of Orientia tsutsugamushi in southwest area of Korea. Am J Trop Med Hyg 84: 250–254.
Jolley KA , Bray JE , Maiden MCJ , 2018. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 3: 124.
Francisco AP , Bugalho M , Ramirez M , Carrico JA , 2009. Global optimal eBURST analysis of multilocus typing data using a graphic matroid approach. BMC Bioinformatics 10: 152.
Jolley KA , Feil E , Chan M-S , Maiden MCJ , 2001. Sequence type analysis and recombinational tests (START). Bioinformatics 17: 1230–1231.
Kumar S , Stecher G , Li M , Knyaz C , Tamura K , 2018. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35: 1547–1549.
Holsinger KE , Weir BS , 2009. Genetics in geographically structured populations: defining, estimating and interpreting FST . Nat Rev Genet 10: 639.
Simpson EH , 1949. Measurement of diversity. Nature 163: 688.
Grundmann H , Hori S , Tanner G , 2001. Determining confidence intervals when measuring genetic diversity and the discriminatory abilities of typing methods for microorganisms. J Clin Microbiol 39: 4190–4192.
Rozas J , Ferrer-Mata A , Sanchez-DelBarrio JC , Guirao-Rico S , Librado P , Ramos-Onsins SE , Sanchez-Gracia A , 2017. DnaSP 6: DNA sequence polymorphism analysis of large data sets. Mol Biol Evol 34: 3299–3302.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 591 | 218 | 27 |
Full Text Views | 133 | 98 | 11 |
PDF Downloads | 99 | 66 | 3 |