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U.S.A."],"published-print":{"date-parts":[[2015,3,17]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Genome sequencing of a multidrug-resistant clinical isolate of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    Typhimurium from a patient that failed ciprofloxacin therapy revealed a mutation in the efflux pump gene,\n                    <jats:italic>acrB<\/jats:italic>\n                    . Computational modelling revealed that the G288D substitution changed the binding of drugs to the distal binding pocket of AcrB. The mutation was recreated in an unrelated\n                    <jats:italic>Salmonella<\/jats:italic>\n                    strain and also in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ; in both species the efflux of ciprofloxacin was increased by the mutation, explaining its resistant phenotype. This is the first time a substitution within an efflux pump protein has been shown to cause drug resistance. Importantly, the finding that one amino acid change can cause resistance to some drugs, but susceptibility to others, informs those developing new antibiotics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1419939112","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T22:22:38Z","timestamp":1425421358000},"page":"3511-3516","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":188,"title":["AcrB drug-binding pocket substitution confers clinically relevant resistance and altered substrate specificity"],"prefix":"10.1073","volume":"112","author":[{"given":"Jessica M. 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