{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:59:43Z","timestamp":1780451983135,"version":"3.54.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Research Program of Korean Disease Control and Prevention Agency","award":["2020E540600"],"award-info":[{"award-number":["2020E540600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>As carbapenem-resistant Acinetobacter baumannii is dominant in clinical settings, the old polymyxin antibiotic colistin has been revived as a therapeutic option. The development of colistin resistance during treatment is becoming a growing concern.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To access low- to mid-level colistin-resistant A. baumannii blood isolates recovered from an outbreak in a tertiary care hospital from a national antimicrobial surveillance study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The entire bacterial genome was sequenced through long-read sequencing methodology. Quantitative RT\u2013PCR was carried out to determine the level of gene expression. Relative growth rates were determined to estimate fitness costs of each isolate caused by the genetic alterations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The A. baumannii isolates belonged to global clone 2 harbouring two intrinsic phosphoethanolamine transferases. Cumulative alterations continuing the colistin resistance were observed. PmrC overproduction caused by the PmrBA226T alteration was identified in A. baumannii isolates with low-level colistin resistance and an additional PmrCR109H substitution led to mid-level colistin resistance. Truncation of the PmrC enzyme by insertion of ISAba59 was compensated by ISAba10-mediated overproduction of EptA and, in the last isolate, the complete PmrAB two-component regulatory system was eliminated to restore the biological cost of the bacterial host.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>During the in-hospital outbreak, a trajectory of genetic modification in colistin-resistant A. baumannii isolates was observed for survival in the harsh conditions imposed by life-threatening drugs with the clear purpose of maintaining drug resistance above a certain level with a reasonable fitness cost.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab363","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T03:12:49Z","timestamp":1631589169000},"page":"69-73","source":"Crossref","is-referenced-by-count":10,"title":["Trajectory of genetic alterations associated with colistin resistance in <i>Acinetobacter baumannii<\/i> during an in-hospital outbreak of infection"],"prefix":"10.1093","volume":"77","author":[{"given":"Eun-Jeong","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea"},{"name":"Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heungjeong","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Jeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea"},{"name":"Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongju","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Rak","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9290-897X","authenticated-orcid":false,"given":"Seok Hoon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea"},{"name":"Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"2022010520142970800_dkab363-B1","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1371\/journal.pgen.0020007","article-title":"Comparative genomics of multidrug resistance in Acinetobacter baumannii","volume":"2","author":"Fournier","year":"2006","journal-title":"PLoS 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system","volume":"53","author":"Adams","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"2022010520142970800_dkab363-B5","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1128\/AAC.00865-13","article-title":"Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii","volume":"57","author":"Pelletier","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2022010520142970800_dkab363-B6","doi-asserted-by":"crossref","first-page":"e00478-15","DOI":"10.1128\/mBio.00478-15","article-title":"Reinforcing lipid A acylation on the cell surface of Acinetobacter baumannii promotes cationic antimicrobial peptide resistance and desiccation survival","volume":"6","author":"Boll","year":"2015","journal-title":"mBio"},{"key":"2022010520142970800_dkab363-B7","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1128\/AAC.00834-10","article-title":"Colistin resistance in Acinetobacter 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operon during colistin therapy of wound infections","volume":"208","author":"Lesho","year":"2013","journal-title":"J Infect Dis"},{"key":"2022010520142970800_dkab363-B16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/jac\/dkp428","article-title":"Global spread of carbapenem-resistant Acinetobacter baumannii","volume":"65","author":"Higgins","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"2022010520142970800_dkab363-B17","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1128\/AAC.01672-09","article-title":"A novel insertion sequence, ISAba10, inserted into ISAba1 adjacent to the blaOXA-23 gene and disrupting the outer membrane protein gene carO in Acinetobacter baumannii","volume":"55","author":"Lee","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2022010520142970800_dkab363-B18","doi-asserted-by":"crossref","first-page":"e01586-18","DOI":"10.1128\/AAC.01586-18","article-title":"Investigation of novel pmrB and eptA mutations 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