{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:23:45Z","timestamp":1789431825133,"version":"build-2803163510"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32-GM008336"],"award-info":[{"award-number":["T32-GM008336"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005895","name":"Fred Hutchinson Cancer Research Center","doi-asserted-by":"publisher","award":["Project Violet"],"award-info":[{"award-number":["Project Violet"]}],"id":[{"id":"10.13039\/100005895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007588","name":"Washington State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007588","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (\n                    <jats:italic>mcr-1<\/jats:italic>\n                    ). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against\n                    <jats:italic>E. coli<\/jats:italic>\n                    #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of\n                    <jats:italic>E. coli<\/jats:italic>\n                    #0346. CDP-B11 with colistin inhibits the growth of\n                    <jats:italic>E. coli<\/jats:italic>\n                    #0346 at\u2009\u2265\u200910\u00d7 lower colistin concentrations compared to colistin alone in Mueller\u2013Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as\n                    <jats:italic>Acinetobacter baumannii, Pseudomonas aeruginosa,<\/jats:italic>\n                    and\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    . In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25\u00a0\u03bcg\/mL) compared to colistin alone (2.5\u00a0\u03bcg\/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2\u00a0h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-81140-8","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T06:06:41Z","timestamp":1611554801000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["In vitro activity of antimicrobial peptide CDP-B11 alone and in combination with colistin against colistin-resistant and multidrug-resistant Escherichia coli"],"prefix":"10.1038","volume":"11","author":[{"given":"Kaitlin S.","family":"Witherell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok D.","family":"Bandaranayake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Call","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"81140_CR1","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/S1473-3099(13)70318-9","volume":"13","author":"R Laxminarayan","year":"2013","unstructured":"Laxminarayan, R. et al. Antibiotic resistance\u2014the need for global solutions. Lancet Infect. Dis. 13, 1057\u20131098 (2013).","journal-title":"Lancet Infect. Dis."},{"key":"81140_CR2","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41579-018-0141-x","volume":"17","author":"M Tyers","year":"2019","unstructured":"Tyers, M. & Wright, G. D. Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat. Rev. Microbiol. 17, 141\u2013155 (2019).","journal-title":"Nat. Rev. Microbiol."},{"key":"81140_CR3","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1592\/phco.30.12.1279","volume":"30","author":"LM Lim","year":"2010","unstructured":"Lim, L. M. et al. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy 30, 1279\u20131291 (2010).","journal-title":"Pharmacotherapy"},{"key":"81140_CR4","first-page":"1","volume":"7","author":"X Wang","year":"2018","unstructured":"Wang, X. et al. Emergence of a novel mobile colistin resistance gene, mcr-8, in NDM-producing Klebsiella pneumoniae. Emerg. Microbes Infect. 7, 1\u20139 (2018).","journal-title":"Emerg. Microbes Infect."},{"key":"81140_CR5","doi-asserted-by":"publisher","first-page":"4856","DOI":"10.1128\/AAC.05996-11","volume":"56","author":"C Vidaillac","year":"2012","unstructured":"Vidaillac, C., Benichou, L. & Duval, R. E. In vitro synergy of colistin combinations against colistin-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae isolates. Antimicrob. Agents Chemother. 56, 4856\u20134861 (2012).","journal-title":"Antimicrob. Agents Chemother."},{"key":"81140_CR6","first-page":"3919","volume":"11","author":"J Lei","year":"2019","unstructured":"Lei, J. et al. The antimicrobial peptides and their potential clinical applications. Am. J. Transl. Res. 11, 3919\u20133931 (2019).","journal-title":"Am. J. Transl. 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