{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:28:01Z","timestamp":1785414481044,"version":"3.56.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["FTT_MLP- 038"],"award-info":[{"award-number":["FTT_MLP- 038"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The escalating threat of antimicrobial resistance (AMR), particularly among gram-negative pathogens, necessitates the development of novel therapeutic agents. Tridecaptins, a class of non-ribosomally synthesized lipopeptides with a novel mode of action, have garnered renewed interest in the fight against AMR. Our group previously identified tridecaptin M, a compound with a promising safety profile, prompting further investigation into its efficacy and preclinical characteristics. Here, we show that tridecaptin M exhibits potent activity against multidrug-resistant (MDR)\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      without cross-resistance to colistin. It effectively inhibits biofilm formation and disrupts 50% of established biofilm at 10\u202f\u00b5g\/mL. Tridecaptin M demonstrates a favorable safety profile, as it does not inhibit the cardiac hERG channel and shows minimal interaction with cytochrome P450 enzymes, with no IC\u2085\u2080 detected up to 44.6\u202f\u00b5g\/mL.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      toxicity studies via subcutaneous administration confirm its safety up to 600\u202fmg\/kg, whereas intravenous administration reveals acute toxicity at \u226530 \u202fmg\/kg, with biochemical evidence of skeletal muscle, cardiac, and hepatic involvement. In mouse infection models using a colistin-resistant MDR strain of\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      reveal the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      potential of tridecaptin M and a dose-dependent efficacy at 10 mg\/kg, 20 mg\/kg, 50 mg\/kg, and 100 mg\/kg doses, showing a non-linear relationship. Tridecaptin M is metabolized by liver microsomes, with low clearance, and pharmacokinetic analysis in rats indicates favorable attributes, with a terminal half-life (T\u2081\/\u2082) of 3.65\u202fh intravenously and 8.81\u202fh subcutaneously. Collectively, these data support the continued preclinical development of tridecaptin M as a promising candidate for treating severe gram-negative infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01083-25","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T18:26:29Z","timestamp":1757615189000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical evaluation of tridecaptin M:\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    efficacy against colistin-resistant Gram-negative bacterial pathogens and pharmacokinetics"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-0015","authenticated-orcid":false,"given":"Vrushali","family":"Raka","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055rjs771","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Microbiology & Antimicrobial Research Laboratory, CSIR-Institute of Microbial Technology","place":["Chandigarh, India"]},{"id":[{"id":"https:\/\/ror.org\/053rcsq61","id-type":"ROR","asserted-by":"publisher"}],"name":"Academy of Scientific & Innovative Research (AcSIR)","place":["Ghaziabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Jangra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055rjs771","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Microbiology & Antimicrobial Research Laboratory, CSIR-Institute of Microbial Technology","place":["Chandigarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parminder","family":"Kaur","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055rjs771","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Microbiology & Antimicrobial Research Laboratory, CSIR-Institute of Microbial Technology","place":["Chandigarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajneesh","family":"Dadwal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055rjs771","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Microbiology & Antimicrobial Research Laboratory, CSIR-Institute of Microbial Technology","place":["Chandigarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8633-3348","authenticated-orcid":true,"given":"Shubhangi","family":"Kansal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/009nfym65","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research","place":["Chandigarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Angrup","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/009nfym65","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research","place":["Chandigarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallab","family":"Ray","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/009nfym65","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research","place":["Chandigarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-6355","authenticated-orcid":true,"given":"Hemraj","family":"Nandanwar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/055rjs771","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Microbiology & Antimicrobial Research Laboratory, CSIR-Institute of Microbial Technology","place":["Chandigarh, India"]},{"id":[{"id":"https:\/\/ror.org\/053rcsq61","id-type":"ROR","asserted-by":"publisher"}],"name":"Academy of Scientific & Innovative Research (AcSIR)","place":["Ghaziabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"World Health Organization. 2025. 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