{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:36:05Z","timestamp":1785418565103,"version":"3.56.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFD1800105"],"award-info":[{"award-number":["2023YFD1800105"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32373069"],"award-info":[{"award-number":["32373069"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Antimicrobial resistance poses a significant global public health challenge in the 21st century, with multidrug resistance in gram-negative bacteria being particularly severe. Colistin (COL) is considered the \u201clast-resort\u201d for treating such infections. Still, its efficacy is significantly reduced due to the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Based on the synergistic antibacterial mechanism between the anthelmintic rafoxanide (RAF) and COL, we synthesized a novel RAF derivative (named as dikalisuan) through a carboxymethylation method, and its structure was confirmed using\n                      <jats:sup>1<\/jats:sup>\n                      H NMR,\n                      <jats:sup>13<\/jats:sup>\n                      C NMR, and HRMS.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      evaluation indicated that the derivatized product had no antibacterial activity (minimum inhibitory concentration [MIC] &gt; 512 \u00b5g\/mL). However, when used in combination with COL, it showed a significantly synergistic effect (fractional inhibitory concentration index [FICI] &lt; 0.5) on\n                      <jats:italic toggle=\"yes\">mcr-1-<\/jats:italic>\n                      positive and -negative resistant strains, including\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      . Notably, the synergistic bactericidal effect was optimal at a moderate concentration of 8 \u03bcg\/mL. Furthermore, within the concentration range of 2 to 128 \u03bcg\/mL, dikalisuan alone or in combination with COL (2 \u03bcg\/mL) showed no significant hemolysis of red blood cells or cytotoxicity. This derivative provides a new strategy for developing adjuvants against multidrug-resistant bacteria and lays the foundation for the structural modification of anthelmintic salicylanilides.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Antimicrobial resistance in gram-negative bacteria is a critical global health threat, with colistin (COL) being a \u201clast-resort\u201d treatment. However, rising resistance has blunted its effectiveness. This study developed a new derivative of rafoxanide (RAF). While this new compound itself is not antibacterial, it effectively potentiates COL\u2019s power against resistant bacteria when used in combination. This strategy offers a promising approach to extend the lifespan of our current antibiotics and provides a new weapon in the fight against difficult-to-treat drug-resistant bacteria.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03612-25","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:00:56Z","timestamp":1774872056000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and synergistic antibacterial activity of rafoxanide derivative as a novel drug for potentiating colistin activity"],"prefix":"10.1128","volume":"14","author":[{"given":"Haotian","family":"Shao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04eq83d71","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Veterinary Medicine, Henan Agricultural University","place":["Zhengzhou, 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