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The recent emergence of polymyxin-resistant bacteria, however, urgently demands clinical optimisation of polymyxin use to minimise further evolution of resistance. In this study we developed a novel combination therapy using minimal concentrations of polymyxin B. After large-scale screening of <jats:italic>Streptomyces<\/jats:italic> secondary metabolites, we identified a reliable polymixin synergist and confirmed as netropsin using high-pressure liquid chromatography, nuclear magnetic resonance and mass spectrometry followed by <jats:italic>in vitro<\/jats:italic> assays using various Gram-negative pathogenic bacteria. To evaluate the effectiveness of combining polymixin B and netropsin <jats:italic>in vivo<\/jats:italic>, we performed survival analysis on greater wax moth <jats:italic>Galleria mellonella<\/jats:italic> infected with colistin-resistant clinical <jats:italic>Acinetobacter baumannii<\/jats:italic> isolates as well as <jats:italic>Escherichia coli, Shigella flexineri, Salmonella typhimuruim,<\/jats:italic> and <jats:italic>Pseudomonas aeruginosa<\/jats:italic>. The survival of infected <jats:italic>G. mellonella<\/jats:italic> was significantly higher when treated with polymyxin B and netropsin in combination than when treated with polymyxin B or netropsin alone. We propose a netropsin combination therapy that minimises the use of polymyxin B when treating infections with multidrug resistant Gram-negative bacteria.<\/jats:p>","DOI":"10.1038\/srep28168","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T10:05:49Z","timestamp":1466071549000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Combination therapy with polymyxin B and netropsin against clinical isolates of multidrug-resistant Acinetobacter baumannii"],"prefix":"10.1038","volume":"6","author":[{"given":"Joon-hui","family":"Chung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhayprasad","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongeun","family":"Yong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Choong-Min","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,6,16]]},"reference":[{"key":"BFsrep28168_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1146\/annurev.biochem.78.082907.145923","volume":"78","author":"H Nikaido","year":"2009","unstructured":"Nikaido, H. 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