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Despite their prevalence, the regulatory mechanisms orchestrating ICE integration and excision remain poorly understood. Here, we investigate the transcriptional regulation of the integrase gene (int) in ICEKp1 of Klebsiella pneumoniae. Our results demonstrate that the integrated ICEKp1 exploits the adjacent host transfer RNA-asn promoter to drive int transcription, whereas the excised ICEKp1 switches to a 3\u2032-end promoter. Remarkably, the messenger RNA stem-loops within the\u00a0int 5\u2032-UTR are organized as a potential terminator, attenuating the total amount of the full-length asn-int transcripts during ICEKp1\u2019s integration. Ligation of the 3\u2032 end and 5\u2032 end of ICEKp1 maintains the activity of the 3\u2032-end promoter for the int transcription in the excised ICEKp1. This promoter switch of the integrase gene promotes a preference for ICEKp1 integration over excision. Furthermore, analogous regulatory mechanisms are observed in ICEclc and ICEEc1, suggesting evolutionary conservation of this regulatory strategy among diverse ICE families. These findings uncover a state-dependent int transcriptional regulatory mechanism that tends ICE toward the integrated state, highlighting the complex interplay between ICEs and their bacterial hosts.<\/jats:p>","DOI":"10.1093\/nar\/gkag254","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:24:11Z","timestamp":1774617851000},"source":"Crossref","is-referenced-by-count":0,"title":["State-dependent promoter switching mediates integrase gene transcription in the integrative and conjugative element ICE\n                    <i>Kp1<\/i>\n                    of\n                    <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1093","volume":"54","author":[{"given":"Guitian","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaizhong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Guangxi Medical University , Nanning 530021 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-7064","authenticated-orcid":false,"given":"Jiahao","family":"Guan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cui","family":"Tai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Guangxi Medical University , Nanning 530021 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjie","family":"Chao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of RNA Innovation, Science and Engineering, Vaccine Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruilan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Guangxi Medical University , Nanning 530021 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-1660","authenticated-orcid":false,"given":"Hong-Yu","family":"Ou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]},{"name":"Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases , Shanghai 200025 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