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Here we show that loss of the regulator SmvR, through adaptation to chlorhexidine, results in increased resistance to a number of cationic biocides in <jats:italic>K. pneumoniae<\/jats:italic> and other members of the Enterobacteriaceae. Clinical Enterobacteriaceae isolates which lack <jats:italic>smvA<\/jats:italic> and <jats:italic>smvR<\/jats:italic> also have an increased susceptibility to chlorhexidine. When <jats:italic>smvA<\/jats:italic> from <jats:italic>Salmonella<\/jats:italic> and <jats:italic>K. pneumoniae<\/jats:italic> are expressed in <jats:italic>Escherichia coli<\/jats:italic>, which lacks a homologue to SmvAR, resistance to chlorhexidine increased (4-fold) but plasmid carriage of <jats:italic>smvA<\/jats:italic> alone was detrimental to the cell. Challenge of <jats:italic>K. pneumoniae<\/jats:italic> with chlorhexidine and another cationic biocide, octenidine, resulted in increased expression of <jats:italic>smvA<\/jats:italic> (approx. 70 fold). Adaptation to octenidine was achieved through mutating key residues in SmvA (A363V; Y391N) rather than abolishing the function of SmvR, as with chlorhexidine adaptation. Molecular modelling was able to predict that octenidine interacted more strongly with these mutated SmvA forms. These results show that SmvA is a major efflux pump for cationic biocides in several bacterial species and that increased efflux through SmvA can lead to increased chlorhexidine and octenidine tolerance.<\/jats:p>","DOI":"10.1038\/s41598-018-37730-0","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T11:04:09Z","timestamp":1549278249000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["SmvA is an important efflux pump for cationic biocides in Klebsiella pneumoniae and other Enterobacteriaceae"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-8869","authenticated-orcid":false,"given":"Matthew E.","family":"Wand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirin","family":"Jamshidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy J.","family":"Bock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-8648","authenticated-orcid":false,"given":"Khondaker Miraz","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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