{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:54:16Z","timestamp":1768485256639,"version":"3.49.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Key Projects of the National Natural Science Foundation of China","award":["41831287"],"award-info":[{"award-number":["41831287"]}]},{"name":"China National Science Fund for Distinguished Young Scholars","award":["41525013"],"award-info":[{"award-number":["41525013"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R & D Program of China","doi-asserted-by":"crossref","award":["2020YFC1806904"],"award-info":[{"award-number":["2020YFC1806904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Projects of Tianjin Natural Science Foundation","award":["19JCZDJC40800"],"award-info":[{"award-number":["19JCZDJC40800"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31870351"],"award-info":[{"award-number":["31870351"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["41907362"],"award-info":[{"award-number":["41907362"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M651016"],"award-info":[{"award-number":["2019M651016"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The msr(E)-mph(E) operon exists widely in diverse species of bacteria and msr(E) and mph(E) genes confer high resistance to macrolides. We aimed to explore whether macrolides regulate the transcription of the operon.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Antibiotic resistance genes in clinical isolates of Klebsiella pneumoniae were analysed by WGS. The transcription of the msr(E)-mph(E) operon was investigated by quantitative PCR. Construction of enhanced green fluorescent protein (eGFP) reporter plasmids, gene knockout and complementation experiments were used to further explore the induction mechanism of macrolides for the operon. Sequence analysis was finally used to investigate whether the operon exists widely in diverse species of bacteria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We originally found that the treatment of a pandrug-resistant isolate of K. pneumoniae (KP1517) with macrolides obviously up-regulated the msr(E)-mph(E) operon, which was further confirmed in another nine clinical isolates of K. pneumoniae. The induction mechanism of macrolides for the operon was partly elucidated. Macrolides could activate the operon promoter, and the J10\/J35 regions (J10: 5\u2032-AGTTATCAT-3\u2032; J35: 5\u2032-TTGTCT-3\u2032) of the promoter were determined. Histone-like nucleoid-structuring protein (HNS) and cAMP receptor protein (CRP) were involved in the erythromycin-mediated activation of the operon promoter. The 476 strains of bacteria carrying the msr(E)-mph(E) operon currently in the NCBI database are mainly Acinetobacter baumannii (158; 33%), K. pneumoniae (95; 20%), Escherichia coli (26; 5%) and Proteus mirabilis (25; 5%). They were mainly isolated from human clinical samples (287; 60%) and had a wide geographical distribution.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Macrolides could activate transcription of the msr(E)-mph(E) operon through HNS and CRP in K. pneumoniae and E. coli, and this might occur in diverse species of bacteria.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab395","type":"journal-article","created":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T19:43:34Z","timestamp":1634413414000},"page":"391-399","source":"Crossref","is-referenced-by-count":6,"title":["Macrolides mediate transcriptional activation of the <i>msr<\/i>(E)-<i>mph<\/i>(E) operon through histone-like nucleoid-structuring protein (HNS) and cAMP receptor protein (CRP)"],"prefix":"10.1093","volume":"77","author":[{"given":"Yitao","family":"Duan","sequence":"first","affiliation":[{"name":"College of Environmental Science and Engineering, Nankai University, Tianjin, China"},{"name":"Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Environmental Science and Engineering, Nankai University, Tianjin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Environmental Science and Engineering, Nankai University, Tianjin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-0129","authenticated-orcid":false,"given":"Daqing","family":"Mao","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Environmental Science and Engineering, Nankai University, Tianjin, China"},{"name":"State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"2022021008132010500_dkab395-B1","author":"Science, AAAS Custom Publishing Office","year":"2021"},{"key":"2022021008132010500_dkab395-B2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1179\/joc.1999.11.2.107","article-title":"The role of newer macrolides in the treatment of community-acquired respiratory tract infection. 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