{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:04:37Z","timestamp":1791443077349,"version":"4.3.3"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100010730","name":"Temasek Life Sciences Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010730","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Saw Swee Hock School of Public Health"},{"name":"Yong Loo Lin School of Medicine"},{"DOI":"10.13039\/501100011744","name":"National University Health System","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009539","name":"Life Sciences Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009539","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012415","name":"Biomedical Research Council","doi-asserted-by":"publisher","award":["03\/1\/27\/18\/216"],"award-info":[{"award-number":["03\/1\/27\/18\/216"]}],"id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["0838\/2004"],"award-info":[{"award-number":["0838\/2004"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012415","name":"Biomedical Research Council","doi-asserted-by":"publisher","award":["05\/1\/21\/19\/425"],"award-info":[{"award-number":["05\/1\/21\/19\/425"]}],"id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012415","name":"Biomedical Research Council","doi-asserted-by":"publisher","award":["11\/1\/21\/19\/678"],"award-info":[{"award-number":["11\/1\/21\/19\/678"]}],"id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The recently discovered tigecycline-inactivating enzyme Tet(X4) can confer high-level tigecycline resistance on its hosts, which makes it a public health concern. This study focused on isolation and screening of Tet(X4)-positive Enterobacteriaceae from the gut microbiota of a cohort of healthy individuals in Singapore.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MinION and Illumina sequencing was performed to obtain the complete genome sequences of Escherichia coli 2EC1-1 and 94EC. Subsequently, 109 human faecal samples were screened retrospectively for eravacycline-resistant Enterobacteriaceae strains, which were further tested for tet(X4) by PCR. The taxonomy of the isolated strains was determined by 16S rRNA gene PCR and Sanger sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Comparative genomic analysis of E. coli 2EC1-1 and 94EC revealed that both carry tet(X4), which is encoded by IncI1-type plasmids p2EC1-1 and p94EC-2, respectively. Retrospective screening of faecal samples collected from 109 healthy individuals showed that the faecal carriage rate of Tet(X4)-producing Enterobacteriaceae is 10.1% (95% CI\u2009=\u20095.1%\u201317.3%), suggesting that tet(X4) is widely distributed in the gut microbiota of healthy individuals in Singapore.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>To the best of our knowledge, this is the first report on the prevalence of tet(X4) in the gut microbiota of a healthy human cohort, as well as the first description of this resistance mechanism outside of China. Our findings suggest that surveillance of tet(X4) in community settings is vital to monitor the spread of this resistance mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaa372","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T07:13:07Z","timestamp":1596611587000},"page":"3480-3484","source":"Crossref","is-referenced-by-count":50,"title":["Emergence of tigecycline- and eravacycline-resistant Tet(X4)-producing Enterobacteriaceae in the gut microbiota of healthy Singaporeans"],"prefix":"10.1093","volume":"75","author":[{"given":"Yichen","family":"Ding","sequence":"first","affiliation":[{"name":"Temasek Life Sciences Laboratory, 1 Research Link, 117604, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woei-Yuh","family":"Saw","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, 3004, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda Wei Lin","family":"Tan","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, 117549, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don Kyin Nwe","family":"Moong","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, 117549, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, A*STAR, 138672, Singapore"},{"name":"NUS Graduate School for Integrative Science and Engineering, National University of Singapore, 119077, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yik Ying","family":"Teo","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, 117549, Singapore"},{"name":"Genome Institute of Singapore, A*STAR, 138672, Singapore"},{"name":"NUS Graduate School for Integrative Science and Engineering, National University of Singapore, 119077, Singapore"},{"name":"Department of Statistics and Applied Probability, National University of Singapore, 117546, Singapore"},{"name":"Life Sciences Institute, National University of Singapore, 117456, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5763-0236","authenticated-orcid":false,"given":"Henning","family":"Seedorf","sequence":"additional","affiliation":[{"name":"Temasek Life Sciences Laboratory, 1 Research Link, 117604, Singapore"},{"name":"Department of Biological Sciences, National University of Singapore, 117558, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"key":"2020111305062772700_dkaa372-B1","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/jac\/dku185","article-title":"Favourable outcome in the treatment of carbapenem-resistant Enterobacteriaceae urinary tract infection with high-dose tigecycline","volume":"69","author":"Brust","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2020111305062772700_dkaa372-B2","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S1473-3099(11)70177-3","article-title":"Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis","volume":"11","author":"Tasina","year":"2011","journal-title":"Lancet Infect Dis"},{"key":"2020111305062772700_dkaa372-B3","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2019.24.25.1900340","article-title":"Detection of plasmid-mediated 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