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Unfortunately, mutations lowering drug affinity for both enzymes are now widespread, rendering these drugs ineffective for many pathogens. To undermine this form of resistance, we examined how bacteria with target alterations differentially cope with fluoroquinolone exposures. We studied this problem in the nosocomial pathogen\n            <jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>\n            , which causes drug-resistant life-threatening infections. Employing genome-wide approaches, we uncovered numerous pathways that could be exploited to raise fluoroquinolone sensitivity independently of target alteration. Remarkably, fluoroquinolone targeting of topo IV in specific mutants caused dramatic hyperinduction of prophage replication and enhanced the mutagenic DNA damage response, but these responses were muted in strains with DNA gyrase as the primary target. This work demonstrates that resistance evolution via target modification can profoundly modulate the antibiotic stress response, revealing potential resistance-associated liabilities.\n          <\/jats:p>","DOI":"10.1128\/mbio.01127-19","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T14:20:12Z","timestamp":1560176412000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["The Landscape of Phenotypic and Transcriptional Responses to Ciprofloxacin in Acinetobacter baumannii: Acquired Resistance Alleles Modulate Drug-Induced SOS Response and Prophage Replication"],"prefix":"10.1128","volume":"10","author":[{"given":"Edward","family":"Geisinger","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Department of Biology, Northeastern University, Boston, 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