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Ongoing research is primarily focused on the development of non-nephrotoxic and -neurotoxic polymyxins as not only standalone agents but also as potentiators that enhance the activity of a partner antibiotic. Safer derivatives of polymyxin B\n                      <jats:sub>3<\/jats:sub>\n                      , a minor component of polymyxin B, were synthesized and utilized as a potentiator of multiple antibiotics. Compound\n                      <jats:bold>1<\/jats:bold>\n                      , consisting of Dap residues, was nontoxic to kidney cells and is a promising outer membrane permeabilizer that synergized with six different classes of antibiotics against MDR Gram-negative bacteria. Compound\n                      <jats:bold>1<\/jats:bold>\n                      extended the activity spectrum of rifampicin, zoliflodacin, and pristinamycin by lowering the minimum inhibitory concentrations of these antibiotics below their interpretative susceptibility breakpoints in MDR\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Enterobacter cloacae<\/jats:italic>\n                      . Notably, the novel combination of zoliflodacin, a first-in-class antibiotic in phase III trials for gonorrhea, and compound\n                      <jats:bold>1<\/jats:bold>\n                      exhibited potent bactericidal activity in MDR\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00712-25","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:00:21Z","timestamp":1758542421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Noncytotoxic polymyxin derivatives enhance antibiotic action against multidrug-resistant Gram-negative bacteria"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0829-3242","authenticated-orcid":false,"given":"Danyel","family":"Ramirez","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gfys938","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danzel Marie","family":"Ramirez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gfys938","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat","family":"Arora","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gfys938","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Arthur","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gfys938","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Medical Genetics, University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-5519","authenticated-orcid":true,"given":"Frank","family":"Schweizer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gfys938","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of Manitoba","place":["Winnipeg, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02gfys938","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology and Infectious Diseases, University of Manitoba","place":["Winnipeg, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3934\/microbiol.2018.3.482"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70318-9"},{"key":"e_1_3_3_4_2","volume-title":"The review on antimicrobial resistance","author":"O\u2019Neill J","year":"2014","unstructured":"O\u2019Neill J. 2014. 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