{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T01:53:00Z","timestamp":1783389180481,"version":"3.54.6"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012833","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224277\/Z\/21\/Z"],"award-info":[{"award-number":["224277\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI144385"],"award-info":[{"award-number":["R21AI144385"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R56AI148645"],"award-info":[{"award-number":["R56AI148645"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Orientia tsutsugamushi<\/jats:italic>\n                    is an obligate intracellular bacterium found in\n                    <jats:italic>Leptotrombidium<\/jats:italic>\n                    mites that causes the human disease scrub typhus. A distinguishing feature of\n                    <jats:italic>O. tsutsugamushi<\/jats:italic>\n                    is its extensive strain diversity, yet differences in virulence between strains are not well defined nor well understood. We sought to determine the bacterial drivers of pathogenicity by comparing seven strains using murine infections combined with epidemiological human data to rank each strain in terms of relative virulence. Murine cytokine expression data revealed that the two most virulent strains, Ikeda and Kato, induced higher levels of IL-6, IL-10, IFN-\u03b3 and MCP-1 than other strains, consistent with increased levels of these cytokines in patients with severe scrub typhus. We sought to identify the mechanistic basis of the observed differential virulence between strains by comparing their genomes,\n                    <jats:italic>in vitro<\/jats:italic>\n                    growth properties and cytokine\/chemokine induction in host cells. We found that there was no single gene or gene group that correlated with virulence, and no clear pattern of\n                    <jats:italic>in vitro<\/jats:italic>\n                    growth rate that predicted disease. However, microscopy-based analysis of the intracellular infection cycle revealed that the only fully avirulent strain in our study, TA686, differed from all the virulent strains in its subcellular localisation and expression of its surface protein ScaC. This leads us to a model whereby drivers of pathogenicity in\n                    <jats:italic>Orientia tsutsugamushi<\/jats:italic>\n                    are distributed throughout the genome, likely in the large and varying arsenal of effector proteins encoded by different strains, and that these interact in complex ways to induce differing immune responses and thus differing disease outcomes in mammalian hosts.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012833","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T13:46:57Z","timestamp":1751291217000},"page":"e1012833","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Comparative virulence analysis of seven diverse strains of Orientia tsutsugamushi reveals a multifaceted and complex interplay of virulence factors responsible for disease"],"prefix":"10.1371","volume":"21","author":[{"given":"Panjaporn","family":"Chaichana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naphat","family":"Satapoomin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitrasak","family":"Kullapanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suthida","family":"Chuenklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manutsanun","family":"Inthawong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Ball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyanate","family":"Sunyakumthorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5802-4580","authenticated-orcid":true,"given":"Jeanne","family":"Salje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"issue":"1","key":"ppat.1012833.ref001","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3390\/tropicalmed3010008","article-title":"A Review of Scrub Typhus (Orientia tsutsugamushi and Related Organisms): Then, Now, and Tomorrow","volume":"3","author":"A Luce-Fedrow","year":"2018","journal-title":"Trop Med Infect Dis"},{"issue":"5","key":"ppat.1012833.ref002","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1097\/00001432-200310000-00009","article-title":"Scrub typhus and tropical rickettsioses","volume":"16","author":"G Watt","year":"2003","journal-title":"Curr Opin Infect Dis"},{"issue":"11","key":"ppat.1012833.ref003","article-title":"A review of the global epidemiology of scrub typhus","volume":"11","author":"G Xu","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"10","key":"ppat.1012833.ref004","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1056\/NEJMoa1603657","article-title":"Endemic Scrub Typhus in South America","volume":"375","author":"T Weitzel","year":"2016","journal-title":"N Engl J Med"},{"issue":"6","key":"ppat.1012833.ref005","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.3201\/eid2506.181860","article-title":"Scrub Typhus in Continental Chile, 2016-20181","volume":"25","author":"T Weitzel","year":"2019","journal-title":"Emerg Infect Dis"},{"issue":"9","key":"ppat.1012833.ref006","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 Chile","volume":"26","author":"K Abarca","year":"2020","journal-title":"Emerg Infect Dis"},{"issue":"12","key":"ppat.1012833.ref007","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":"L Izzard","year":"2010","journal-title":"J Clin Microbiol"},{"issue":"19","key":"ppat.1012833.ref008","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":"N-H Cho","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ppat.1012833.ref009","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":"K Nakayama","year":"2008","journal-title":"DNA Res"},{"key":"ppat.1012833.ref010","article-title":"Long-read whole genome sequencing and comparative analysis of six strains of the human pathogen Orientia tsutsugamushi","author":"EM Batty","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"issue":"6","key":"ppat.1012833.ref011","doi-asserted-by":"crossref","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":"S Giengkam","year":"2023","journal-title":"mSphere"},{"key":"ppat.1012833.ref012","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3389\/fcimb.2014.00186","article-title":"Orientia tsutsugamushi ankyrin repeat-containing protein family members are Type 1 secretion system substrates that traffic to the host cell endoplasmic reticulum","volume":"4","author":"L VieBrock","year":"2015","journal-title":"Front Cell Infect Microbiol"},{"issue":"19","key":"ppat.1012833.ref013","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1128\/JB.00276-15","article-title":"Orientia tsutsugamushi Strain Ikeda Ankyrin Repeat-Containing Proteins Recruit SCF1 Ubiquitin Ligase Machinery via Poxvirus-Like F-Box Motifs","volume":"197","author":"AR Beyer","year":"2015","journal-title":"J Bacteriol"},{"issue":"7","key":"ppat.1012833.ref014","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12727","article-title":"Orientia tsutsugamushi Ank9 is a multifunctional effector that utilizes a novel GRIP-like Golgi localization domain for Golgi-to-endoplasmic reticulum trafficking and interacts with host COPB2","volume":"19","author":"AR Beyer","year":"2017","journal-title":"Cell Microbiol"},{"issue":"5","key":"ppat.1012833.ref015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007023","article-title":"Orientia tsutsugamushi uses two Ank effectors to modulate NF-\u03baB p65 nuclear transport and inhibit NF-\u03baB transcriptional activation","volume":"14","author":"SM Evans","year":"2018","journal-title":"PLoS Pathog"},{"issue":"4","key":"ppat.1012833.ref016","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01816-21","article-title":"Orientia tsutsugamushi Nucleomodulin Ank13 Exploits the RaDAR Nuclear Import Pathway To Modulate Host Cell Transcription","volume":"12","author":"HE Adcox","year":"2021","journal-title":"mBio"},{"issue":"4","key":"ppat.1012833.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0009339","article-title":"Orientia tsutsugamushi modulates cellular levels of NF-\u03baB inhibitor p105","volume":"15","author":"T Wangsanut","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ppat.1012833.ref018","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1038\/s41467-022-31176-9","article-title":"The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state","volume":"13","author":"S Atwal","year":"2022","journal-title":"Nat Commun"},{"issue":"7","key":"ppat.1012833.ref019","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1128\/IAI.01620-05","article-title":"Exploitation of the endocytic pathway by Orientia tsutsugamushi in nonprofessional phagocytes","volume":"74","author":"H Chu","year":"2006","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1012833.ref020","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1128\/IAI.69.1.494-500.2001","article-title":"Microtubule- and dynein-mediated movement of Orientia tsutsugamushi to the microtubule organizing center","volume":"69","author":"SW Kim","year":"2001","journal-title":"Infect Immun"},{"key":"ppat.1012833.ref021","article-title":"The intracellular bacterium Orientia tsutsugamushi hijacks the adaptor protein BICD2 for dynein-based motility","author":"G Manigrasso","year":"2024","journal-title":"Nature Communications (in press)"},{"issue":"3","key":"ppat.1012833.ref022","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1084\/jem.150.3.703","article-title":"Intracellular localization of Rickettsia tsutsugamushi in polymorphonuclear leukocytes","volume":"150","author":"Y Rikihisa","year":"1979","journal-title":"J Exp Med"},{"issue":"1","key":"ppat.1012833.ref023","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":"B Mika-Gospodorz","year":"2020","journal-title":"Nat Commun"},{"key":"ppat.1012833.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0054570","volume-title":"An intradermal inoculation model of scrub typhus in Swiss CD-1 mice demonstrates more rapid dissemination of virulent strains of Orientia tsutsugamushi","author":"P Sunyakumthorn","year":"2013"},{"issue":"11","key":"ppat.1012833.ref025","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1128\/iai.59.11.4134-4141.1991","article-title":"Comparative susceptibility to mouse interferons of Rickettsia tsutsugamushi strains with different virulence in mice and of Rickettsia rickettsii","volume":"59","author":"B Hanson","year":"1991","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1012833.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0011445","article-title":"Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice","volume":"17","author":"JD Thiriot","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"ppat.1012833.ref027","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":"T Enatsu","year":"1999","journal-title":"FEMS Microbiol Lett"},{"issue":"4","key":"ppat.1012833.ref028","first-page":"339","article-title":"Studies on scrib typhus; tsutsugamushi disease; heterogenicity of strains of R. tsutsugamushi as demonstrated by cross-vaccination studies","volume":"87","author":"FL Rights","year":"1948","journal-title":"J Exp Med"},{"issue":"3","key":"ppat.1012833.ref029","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":"SD Blacksell","year":"2008","journal-title":"FEMS Immunol Med Microbiol"},{"issue":"8","key":"ppat.1012833.ref030","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1111\/j.1348-0421.1984.tb00743.x","article-title":"Isolation of Rickettsia tsutsugamushi antigenically different from Kato, Karp, and Gilliam strains from patients","volume":"28","author":"A Tamura","year":"1984","journal-title":"Microbiol Immunol"},{"issue":"2","key":"ppat.1012833.ref031","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/infdis\/134.2.193","article-title":"Clinical response of silvered leaf monkeys (Presbytis cristatus) to infection with strains of Rickettsia tsutsugamushi virulent and avirulent for mice","volume":"134","author":"DM Robinson","year":"1976","journal-title":"J Infect Dis"},{"issue":"4","key":"ppat.1012833.ref032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0011243","article-title":"Genomic bacterial load associated with bacterial genotypes and clinical characteristics in patients with scrub typhus in Hainan Island, Southern China","volume":"17","author":"G Wang","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"ppat.1012833.ref033","article-title":"Differences in clinical features according to Boryoung and Karp genotypes of Orientia tsutsugamushi","volume":"6","author":"D-M Kim","year":"2011","journal-title":"PLoS One"},{"issue":"7","key":"ppat.1012833.ref034","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.micinf.2011.03.003","article-title":"Subversion of host cell signaling by Orientia tsutsugamushi","volume":"13","author":"Y Ge","year":"2011","journal-title":"Microbes Infect"},{"key":"ppat.1012833.ref035","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.3389\/fmicb.2019.02065","article-title":"Scrub Typhus Pathogenesis: Innate Immune Response and Lung Injury During Orientia tsutsugamushi Infection","volume":"10","author":"B Trent","year":"2019","journal-title":"Front Microbiol"},{"key":"ppat.1012833.ref036","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ijid.2022.12.022","article-title":"Multiple Orientia clusters and Th1-skewed chemokine profile: a cross-sectional study in patients with scrub typhus from Nepal","volume":"128","author":"CC-S M\u00fcnch","year":"2023","journal-title":"Int J Infect Dis"},{"issue":"2","key":"ppat.1012833.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002648","article-title":"Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality","volume":"8","author":"E Astrup","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"ppat.1012833.ref038","article-title":"Increased level and interferon-\u03b3 production of circulating natural killer cells in patients with scrub typhus","volume":"11","author":"S-J Kang","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"ppat.1012833.ref039","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1128\/jcm.35.12.3320-3322.1997","article-title":"Increased levels of macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha in sera of patients with Orientia tsutsugamushi infection","volume":"35","author":"H Iwasaki","year":"1997","journal-title":"J Clin Microbiol"},{"issue":"2","key":"ppat.1012833.ref040","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.clim.2004.08.006","article-title":"Differential expression of interferon-gamma and interferon-gamma-inducing cytokines in Thai patients with scrub typhus or leptospirosis","volume":"113","author":"W Chierakul","year":"2004","journal-title":"Clin Immunol"},{"issue":"2","key":"ppat.1012833.ref041","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3390\/pathogens10020228","article-title":"Significant Growth by Rickettsia Species within Human Macrophage-Like Cells Is a Phenotype Correlated with the Ability to Cause Disease in Mammals","volume":"10","author":"MN Kristof","year":"2021","journal-title":"Pathogens"},{"key":"ppat.1012833.ref042","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fcimb.2016.00080","article-title":"Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells","volume":"6","author":"P Curto","year":"2016","journal-title":"Front Cell Infect Microbiol"},{"issue":"5","key":"ppat.1012833.ref043","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012020","article-title":"Lack of the IFN-\u03b3 signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions","volume":"20","author":"Y Liang","year":"2024","journal-title":"PLoS Pathog"},{"issue":"5","key":"ppat.1012833.ref044","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41564-020-0673-5","article-title":"Inflammasome-mediated antagonism of type I interferon enhances Rickettsia pathogenesis","volume":"5","author":"TP Burke","year":"2020","journal-title":"Nat Microbiol"},{"key":"ppat.1012833.ref045","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.67029","article-title":"Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis","volume":"10","author":"TP Burke","year":"2021","journal-title":"Elife"},{"issue":"2","key":"ppat.1012833.ref046","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1089\/vbz.2015.1831","article-title":"Prevalence and Phylogenetic Analysis of Orientia tsutsugamushi in Small Mammals in Hanoi, Vietnam","volume":"16","author":"K Hotta","year":"2016","journal-title":"Vector Borne Zoonotic Dis"},{"key":"ppat.1012833.ref047","doi-asserted-by":"crossref","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":"JF Cosson","year":"2015","journal-title":"Parasit Vectors"},{"issue":"6","key":"ppat.1012833.ref048","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1348-0421.2001.tb02643.x","article-title":"Epidemiological survey of Orientia tsutsugamushi distribution in field rodents in Saitama Prefecture, Japan, and discovery of a new type","volume":"45","author":"A Tamura","year":"2001","journal-title":"Microbiol Immunol"},{"key":"ppat.1012833.ref049","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1749-6632.1975.tb35090.x","article-title":"Attempts to infect and demonstrate transovarial transmission of R. tsutsugamushi in three species of Leptotrombidium mites","volume":"266","author":"JS Walker","year":"1975","journal-title":"Ann N Y Acad Sci"},{"issue":"8","key":"ppat.1012833.ref050","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s41564-022-01169-x","article-title":"The evolutionary origin of host association in the Rickettsiales","volume":"7","author":"ME Sch\u00f6n","year":"2022","journal-title":"Nat Microbiol"},{"key":"ppat.1012833.ref051","article-title":"Metagenome diversity illuminates origins of pathogen effectors","author":"VI Verhoeve","year":"2023","journal-title":"bioRxiv"},{"key":"ppat.1012833.ref052","doi-asserted-by":"crossref","first-page":"104818","DOI":"10.1016\/j.meegid.2021.104818","article-title":"Targeted capture and sequencing of Orientia tsutsugamushi genomes from chiggers and humans","volume":"91","author":"I Elliott","year":"2021","journal-title":"Infect Genet Evol"},{"issue":"8","key":"ppat.1012833.ref053","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.3201\/eid2908.230528","article-title":"Detection of Orientia spp. Bacteria in Field-Collected Free-Living Eutrombicula Chigger Mites, United States","volume":"29","author":"K Chen","year":"2023","journal-title":"Emerg Infect Dis"},{"key":"ppat.1012833.ref054","article-title":"Orientia tsutsugamushi: analysis of the mobilome of a highly fragmented and repetitive genome reveals ongoing lateral gene transfer in an obligate intracellular bacterium","author":"G Giengkam","year":"2023","journal-title":"mSphere"},{"issue":"8","key":"ppat.1012833.ref055","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004009","article-title":"Improved Quantification, Propagation, Purification and Storage of the Obligate Intracellular Human Pathogen Orientia tsutsugamushi","volume":"9","author":"S Giengkam","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1012833.ref056","author":"J Salje","year":"2025"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012833","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012833","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T15:32:47Z","timestamp":1751988767000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012833"}},"subtitle":[],"editor":[{"given":"Jason A","family":"Carlyon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012833","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.18.629091","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}