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To counteract the latter activity, bacteriophage \u03bb encodes a small protein inhibitor called Gam that binds to RecBCD and inactivates the complex. Here, we show that Gam inhibits RecBCD by competing at the DNA-binding site. The interaction surface is extensive and involves molecular mimicry of the DNA substrate. We also show that expression of Gam in\n                    <jats:italic>E. coli<\/jats:italic>\n                    or\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    increases sensitivity to fluoroquinolones; antibacterials that kill cells by inhibiting topoisomerases and inducing double-stranded DNA breaks. Furthermore, fluoroquinolone-resistance in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    clinical isolates is reversed by expression of Gam. Together, our data explain the synthetic lethality observed between topoisomerase-induced DNA breaks and the RecBCD gene products, suggesting a new co-antibacterial strategy.\n                  <\/jats:p>","DOI":"10.7554\/elife.22963","type":"journal-article","created":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T10:59:55Z","timestamp":1482490795000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.22963","source":"Crossref","is-referenced-by-count":63,"title":["Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones"],"prefix":"10.7554","volume":"5","author":[{"given":"Martin","family":"Wilkinson","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Structural Biology, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca A","family":"Troman","sequence":"additional","affiliation":[{"name":"School of Biochemistry, University of Bristol","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan AK","family":"Wan Nur Ismah","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriy","family":"Chaban","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Structural Biology, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B","family":"Avison","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4612-7141","authenticated-orcid":true,"given":"Mark 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