{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T09:01:59Z","timestamp":1779872519878,"version":"3.53.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"10","funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1ZIAHL001056"],"award-info":[{"award-number":["1ZIAHL001056"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM126363"],"award-info":[{"award-number":["R01 GM126363"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI170546"],"award-info":[{"award-number":["R01 AI170546"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1FI2GM142536"],"award-info":[{"award-number":["1FI2GM142536"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1FI2GM142536"],"award-info":[{"award-number":["1FI2GM142536"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["ZIAHL001056"],"award-info":[{"award-number":["ZIAHL001056"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The type II topoisomerases, gyrase and topoisomerase IV, are ubiquitous enzymes in bacteria that help regulate DNA topology and are the molecular targets of fluoroquinolone antibacterials. As part of their catalytic mechanism, these enzymes transiently cleave DNA in a sequence-dependent manner. Determining the extent to which various factors influence the sequence-dependent cleavage of these enzymes, particularly across bacterial species, could help reveal important insights into their physiological functions and guide the development of new, more effective antibacterials. Here, we used our recently developed SHAN-seq method to map and compare the DNA cleavage site preferences of gyrases and topoisomerase IVs from three different pathogenic bacterial species, Escherichia coli, Bacillus anthracis, and Mycobacterium tuberculosis, in the presence of the fluoroquinolone, ciprofloxacin. We found that the enzymes\u2019 cleavage specificities vary across bacterial species, with DNA supercoil chirality, and in response to ciprofloxacin. Our findings suggest that subtle variations in the enzymes\u2019 catalytic core and C-terminal domains alter their cleavage site preferences, which could, in turn, influence their physiological activities and susceptibility to fluoroquinolone antibacterials.<\/jats:p>","DOI":"10.1093\/nar\/gkag527","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:05:13Z","timestamp":1778760313000},"source":"Crossref","is-referenced-by-count":0,"title":["Bacterial type II topoisomerases cleave DNA in a species-specific manner"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6883","authenticated-orcid":false,"given":"Ian L","family":"Morgan","sequence":"first","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey Y","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5954-0763","authenticated-orcid":false,"given":"Jillian F","family":"Armenia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2550-4884","authenticated-orcid":false,"given":"Neil","family":"Osheroff","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]},{"name":"Department of Medicine (Hematology\/Oncology), Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-5671","authenticated-orcid":false,"given":"Keir C","family":"Neuman","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"2026052704030815900_B1","doi-asserted-by":"publisher","first-page":"2000286","DOI":"10.1002\/bies.202000286","article-title":"DNA topoisomerases: advances in understanding of cellular roles and multi-protein complexes via structure-function analysis","volume":"43","author":"McKie","year":"2021","journal-title":"Bioessays"},{"key":"2026052704030815900_B2","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/978-3-319-78538-7","article-title":"Bacterial type II topoisomerases and target-mediated drug resistance","volume-title":"Antimicrobial Resistance in the 21st Century","author":"Gibson","year":"2018"},{"key":"2026052704030815900_B3","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1021\/acsinfecdis.4c00128","article-title":"Gyrase and topoisomerase IV: recycling old targets for new antibacterials to combat fluoroquinolone resistance","volume":"10","author":"Collins","year":"2024","journal-title":"ACS Infect Dis"},{"key":"2026052704030815900_B4","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/nrm3228","article-title":"All tangled up: how cells direct, manage and exploit topoisomerase function","volume":"12","author":"Vos","year":"2011","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026052704030815900_B5","doi-asserted-by":"publisher","first-page":"11199","DOI":"10.3390\/ijms241311199","article-title":"Telling your right hand from your left: the effects of DNA supercoil handedness on the actions of type II 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