{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T20:24:47Z","timestamp":1775766287357,"version":"3.50.1"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R35ES028343"],"award-info":[{"award-number":["R35ES028343"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institutes of General Medical Sciences","doi-asserted-by":"crossref","award":["2RM1GM130450"],"award-info":[{"award-number":["2RM1GM130450"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The acquisition of multidrug resistance by pathogenic bacteria is a potentially incipient pandemic. Horizontal transfer of DNA from mobile integrative conjugative elements (ICEs) provides an important way to introduce genes that confer antibiotic (Ab)-resistance in recipient cells. Sizable numbers of SXT\/R391 ICEs encode a hypermutagenic Rum DNA polymerase (Rum pol), which has significant homology with Escherichia coli pol V. Here, we show that even under tight transcriptional and post-transcriptional regulation imposed by host bacteria and the R391 ICE itself, Rum pol rapidly accelerates development of multidrug resistance (CIPR, RifR, AmpR) in E. coli in response to SOS-inducing Ab and non-Ab external stressors bleomycin (BLM), ciprofloxacin (CIP) and UV radiation. The impact of Rum pol on the rate of acquisition of drug resistance appears to surpass potential contributions from other cellular processes. We have shown that RecA protein plays a central role in controlling the ability of Rum pol to accelerate antibiotic resistance. A single amino acid substitution in RecA, M197D, acts as a \u2018Master Regulator\u2019 that effectively eliminates the Rum pol-induced Ab resistance. We suggest that Rum pol should be considered as one of the major factors driving development of de novo Ab resistance in pathogens carrying SXT\/R391 ICEs.<\/jats:p>","DOI":"10.1093\/nar\/gkae899","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T18:00:00Z","timestamp":1729101600000},"page":"12987-13002","source":"Crossref","is-referenced-by-count":2,"title":["Pathogen-encoded Rum DNA polymerase drives rapid bacterial drug resistance"],"prefix":"10.1093","volume":"52","author":[{"given":"Malgorzata\u00a0M","family":"Jaszczur","sequence":"first","affiliation":[{"name":"University of Southern California Department of Biological Sciences, , Los Angeles , CA 90089 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8802-2188","authenticated-orcid":false,"given":"Phuong","family":"Pham","sequence":"additional","affiliation":[{"name":"University of Southern California Department of Biological Sciences, , Los Angeles , CA 90089 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debika","family":"Ojha","sequence":"additional","affiliation":[{"name":"University of Southern California Department of Biological Sciences, , Los Angeles , CA 90089 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia\u00a0Q","family":"Pham","sequence":"additional","affiliation":[{"name":"University of Southern California Department of Biological Sciences, , Los Angeles , CA 90089 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John\u00a0P","family":"McDonald","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health , Bethesda , MD 20892 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Woodgate","sequence":"additional","affiliation":[{"name":"Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health , Bethesda , MD 20892 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-3284","authenticated-orcid":false,"given":"Myron\u00a0F","family":"Goodman","sequence":"additional","affiliation":[{"name":"University of Southern California Department of Biological Sciences, , Los Angeles , CA 90089 ,","place":["USA"]},{"name":"University of Southern California Department of Chemistry, , Los Angeles , Los Angeles , CA 90089 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"2025062419104314300_B1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/S0140-6736(22)00087-3","article-title":"The overlooked pandemic of antimicrobial resistance","volume":"399","author":"Laxminarayan","year":"2022","journal-title":"Lancet"},{"key":"2025062419104314300_B2","first-page":"2019","article-title":"Centers for disease control and prevention: antibiotic resistance threats in the United States","author":"CDC","year":"2019"},{"key":"2025062419104314300_B3","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.cell.2007.03.004","article-title":"Molecular mechanisms of antibacterial multidrug resistance","volume":"128","author":"Alekshun","year":"2007","journal-title":"Cell"},{"key":"2025062419104314300_B4","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41579-021-00650-4","article-title":"Horizontal gene transfer and adaptive evolution in bacteria","volume":"20","author":"Arnold","year":"2022","journal-title":"Nat. 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