{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:35:50Z","timestamp":1791930950936,"version":"4.3.4"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T00:00:00Z","timestamp":1724457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was funded through an intramural grant","award":["MI01798G"],"award-info":[{"award-number":["MI01798G"]}]},{"DOI":"10.13039\/501100007488","name":"Indian Institute of Technology Delhi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The genomic landscape associated with early adaptation to ciprofloxacin is poorly understood. Although the interplay between core metabolism and antimicrobial resistance is being increasingly recognized, mutations in metabolic genes and their biological role remain elusive. Here, we exposed Escherichia coli to increasing gradients of ciprofloxacin with intermittent transfer-bottlenecking and identified mutations in three non-canonical targets linked to metabolism including a deletion (tRNA-Arg\u0394414-bp) and point mutations in the regulatory regions of argI (ARG box) and narU. Our findings suggest that these mutations modulate arginine and carbohydrate metabolism, facilitate anaerobiosis and increased ATP production during ciprofloxacin stress. Furthermore, mutations in the regulatory regions of argI and narU were detected in over 70% of sequences from clinical E. coli isolates and were overrepresented among ciprofloxacin-resistant isolates. In sum, we have identified clinically relevant mutations in the regulatory regions of metabolic genes as a central theme that drives physiological changes necessary for adaptation to ciprofloxacin stress.<\/jats:p>","DOI":"10.1093\/nar\/gkae719","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T15:49:57Z","timestamp":1724514597000},"page":"10385-10399","source":"Crossref","is-referenced-by-count":4,"title":["Clinically relevant mutations in regulatory regions of metabolic genes facilitate early adaptation to ciprofloxacin in <i>Escherichia coli<\/i>"],"prefix":"10.1093","volume":"52","author":[{"given":"Arijit","family":"Pal","sequence":"first","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"},{"name":"Department of Zoology, Raiganj Surendranath Mahavidyalaya, Sudarshanpur , Raiganj , Uttar Dinajpur, West Bengal 733134 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipannita","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratyusha","family":"Thakur","sequence":"additional","affiliation":[{"name":"RNA Biology Laboratory, Department of Chemistry, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Nagpal","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhumathi","family":"Irulappan","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Christian Medical College , Vellore , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Maruthan","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Christian Medical College , Vellore , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanket","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5237-6074","authenticated-orcid":false,"given":"Nikita\u00a0G","family":"Patil","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"},{"name":"Amity Institute of Virology and Immunology, Amity University , Noida , Uttar Pradesh , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6575-1599","authenticated-orcid":false,"given":"Tanmay","family":"Dutta","sequence":"additional","affiliation":[{"name":"RNA Biology Laboratory, Department of Chemistry, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Veeraraghavan","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Christian Medical College , Vellore , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0530-9851","authenticated-orcid":false,"given":"Perumal","family":"Vivekanandan","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences, Indian Institute of Technology Delhi , Hauz Khas, New Delhi\u00a0 110016 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,24]]},"reference":[{"key":"2024092307463651600_B1","doi-asserted-by":"crossref","first-page":"1025633","DOI":"10.3389\/fpubh.2022.1025633","article-title":"The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic","volume":"10","author":"Shariati","year":"2022","journal-title":"Front. 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