{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:18:24Z","timestamp":1789859904904,"version":"4.0.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We used classical mutagens in Gram-negative\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            to study synergies with different classes of antibiotics, test models of antibiotic mechanisms of action, and examine the basis of synergy. We used 4-nitroquinoline 1-oxide (4NQO), zebularine (ZEB), 5-azacytidine (5AZ), 2-aminopurine (2AP), and 5-bromodeoxyuridine (5BrdU) as mutagens (with bactericidal potency of 4NQO &gt; ZEB &gt; 5AZ &gt; 2AP &gt; 5BrdU) and vancomycin (VAN), ciprofloxacin (CPR), trimethoprim (TMP), gentamicin (GEN), tetracycline (TET), erythromycin (ERY), and chloramphenicol (CHL) as antibiotics. We detected the strongest synergies with 4NQO, an agent that oxidizes guanines and ultimately results in double-strand breaks when paired with the bactericidal antibiotics VAN, TMP, CPR, and GEN, but no synergies with the bacteriostatic antibiotics TET, ERY, and CHL. Each of the other mutagens displays synergies with the bactericidal antibiotics to various degrees that reflect their potencies, as well as with some of the other mutagens. The results support recent models showing that bactericidal antibiotics kill bacteria principally by ultimately generating more double-strand breaks than can be repaired. We discuss the synergies seen here and elsewhere as representing dose effects of not the proximal target damage but rather the ultimate resulting double-strand breaks. We also used the results of pairwise tests to place the classic mutagens into functional antibacterial categories within a previously defined drug interaction network.\n          <\/jats:p>","DOI":"10.1128\/aac.02485-15","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T22:23:15Z","timestamp":1451341395000},"page":"1515-1520","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Exploring Synergy between Classic Mutagens and Antibiotics To Examine Mechanisms of Synergy and Antibiotic Action"],"prefix":"10.1128","volume":"60","author":[{"given":"Lisa Yun","family":"Song","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina Manzhu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA"},{"name":"David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.004"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7401022"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1755"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(86)90490-0"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03502-14"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1128\/JCM.01284-07","article-title":"Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004","volume":"45","author":"Lockhardt SR","year":"2007","unstructured":"Lockhardt SR, Abramson MA, Beekmann SE, Gallagher G, Riedel S, Diekema DJ, Quinn JP, Doern GV. 2007. 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