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All rights reserved.","name":"copyright","label":"Copyright"}]},{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T08:25:23Z","timestamp":1772094323273,"version":"3.50.1"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM112757"],"award-info":[{"award-number":["GM112757"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015911","name":"Joint Genome Institute","doi-asserted-by":"publisher","award":["2817"],"award-info":[{"award-number":["2817"]}],"id":[{"id":"10.13039\/100015911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Ionizing radiation (IR) is lethal to most organisms at high doses, damaging every cellular macromolecule via induction of reactive oxygen species (ROS). Utilizing experimental evolution and continuing previous work, we have generated the most IR-resistant <jats:italic>Escherichia coli<\/jats:italic> populations developed to date. After 100 cycles of selection, the dose required to kill 99% the four replicate populations (IR9-100, IR10-100, IR11-100, and IR12-100) has increased from 750 Gy to approximately 3,000 Gy. Fitness trade-offs, specialization, and clonal interference are evident. Long-lived competing sub-populations are present in three of the four lineages. In IR9, one lineage accumulates the heme precursor, porphyrin, leading to generation of yellow-brown colonies. Major genomic alterations are present. IR9 and IR10 exhibit major deletions and\/or duplications proximal to the chromosome replication terminus. Contributions to IR resistance have expanded beyond the alterations in DNA repair systems documented previously. Variants of proteins involved in ATP synthesis (AtpA), iron-sulfur cluster biogenesis (SufD) and cadaverine synthesis (CadA) each contribute to IR resistance in IR9-100. Major genomic and physiological changes are emerging. An isolate from IR10 exhibits protein protection from ROS similar to the extremely radiation resistant bacterium <jats:italic>Deinococcus radiodurans<\/jats:italic>, without evident changes in cellular metal homeostasis. Selection is continuing with no limit to IR resistance in evidence as our <jats:italic>E. coli<\/jats:italic> populations approach levels of IR resistance typical of <jats:italic>D. radiodurans<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fmicb.2020.582590","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T05:22:03Z","timestamp":1600752123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Physiology of Highly Radioresistant Escherichia coli After Experimental Evolution for 100 Cycles of Selection"],"prefix":"10.3389","volume":"11","author":[{"given":"Steven T.","family":"Bruckbauer","sequence":"first","affiliation":[]},{"given":"Joel","family":"Martin","sequence":"additional","affiliation":[]},{"given":"Benjamin B.","family":"Minkoff","sequence":"additional","affiliation":[]},{"given":"Mike T.","family":"Veling","sequence":"additional","affiliation":[]},{"given":"Illissa","family":"Lancaster","sequence":"additional","affiliation":[]},{"given":"Jessica","family":"Liu","sequence":"additional","affiliation":[]},{"given":"Joseph D.","family":"Trimarco","sequence":"additional","affiliation":[]},{"given":"Brian","family":"Bushnell","sequence":"additional","affiliation":[]},{"given":"Anna","family":"Lipzen","sequence":"additional","affiliation":[]},{"given":"Elizabeth A.","family":"Wood","sequence":"additional","affiliation":[]},{"given":"Michael R.","family":"Sussman","sequence":"additional","affiliation":[]},{"given":"Christa","family":"Pennacchio","sequence":"additional","affiliation":[]},{"given":"Michael M.","family":"Cox","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1118\/1.598691","article-title":"AAPM\u2019s TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.","volume":"26","author":"Almond","year":"1999","journal-title":"Med. 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All rights reserved.","name":"copyright","label":"Copyright"}]},{"indexed":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T15:16:36Z","timestamp":1649085396659},"publisher":"Office of Scientific and Technical Information (OSTI)","award-start":{"date-parts":[[2016,5,12]]},"award":"2817","DOI":"10.46936\/10.25585\/60000600","type":"grant","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T19:07:33Z","timestamp":1630523253000},"source":"Crossref","prefix":"10.46936","member":"960","project":[{"project-title":[{"title":"Molecular basis of extreme resistance to ionizing radiation in evolved populations of Escherichia coli"}],"lead-investigator":[{"given":"Michael","family":"Cox","affiliation":[]}],"funding":[{"type":"award","funder":{"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"publisher"}],"name":"US Department of Energy"}}]}],"deposited":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T02:52:19Z","timestamp":1633747939000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/www.osti.gov\/award-doi-service\/biblio\/10.46936\/10.25585\/60000600"}},"issued":{"date-parts":[[2016,5,12]]},"URL":"https:\/\/doi.org\/10.46936\/10.25585\/60000600"},{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T03:35:26Z","timestamp":1775273726114,"version":"3.50.1"},"reference-count":91,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T00:00:00Z","timestamp":1555286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Department of Energy Joint Genome Institute","award":["2817"],"award-info":[{"award-number":["2817"]}]},{"name":"Department of Energy Joint Genome Institute","award":["502930"],"award-info":[{"award-number":["502930"]}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM112757"],"award-info":[{"award-number":["GM112757"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2019,4,15]]},"abstract":"<jats:p>\n            Some bacterial species exhibit astonishing resistance to ionizing radiation, with\n            <jats:named-content content-type=\"genus-species\">Deinococcus radiodurans<\/jats:named-content>\n            being the archetype. As natural IR sources rarely exceed mGy levels, the capacity of\n            <jats:italic>Deinococcus<\/jats:italic>\n            to survive 5,000\u2009Gy has been attributed to desiccation resistance. To understand the molecular basis of true extreme IR resistance, we are using experimental evolution to generate strains of\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            with IR resistance levels comparable to\n            <jats:italic>Deinococcus<\/jats:italic>\n            . Experimental evolution has previously generated moderate radioresistance for multiple bacterial species. However, these efforts could not take advantage of modern genomic sequencing technologies. In this report, we examine four replicate bacterial populations after 50 selection cycles. Genomic sequencing allows us to follow the genesis of mutations in populations throughout selection. Novel mutations affecting genes encoding DNA repair proteins and RNA polymerase enhance radioresistance. However, more contributors are apparent.\n          <\/jats:p>","DOI":"10.1128\/jb.00784-18","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T13:22:59Z","timestamp":1548768179000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Experimental Evolution of Extreme Resistance to Ionizing Radiation in\n            <i>Escherichia coli<\/i>\n            after 50 Cycles of Selection"],"prefix":"10.1128","volume":"201","author":[{"given":"Steven T.","family":"Bruckbauer","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}]},{"given":"Joseph D.","family":"Trimarco","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"},{"name":"Duke Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, 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