{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T22:46:32Z","timestamp":1765233992282,"version":"3.41.0"},"reference-count":8,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Innovative Medicines Initiative 2 Joint Undertaking","award":["853979"],"award-info":[{"award-number":["853979"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>NOSO-502 belongs to a new class of cationic peptide antimicrobials\u2014the odilorhabdins\u2014which have a novel mechanism of action inhibiting protein synthesis. NOSO-502 is in preclinical development for the treatment of difficult-to-treat MDR Gram-negative infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 360 Enterobacterales were tested against NOSO-502 and comparators using the ISO reference microdilution method. The test panel was derived from clinical isolates and enriched with MDR strains including carbapenemase producers. Time\u2013kill experiments were performed with NOSO-502 and two comparator agents over 24\u2005h at MIC\u00d71 to MIC\u00d716 concentrations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>NOSO-502 demonstrated potent in vitro activity against Escherichia coli (MIC50\/90 2\/4\u2005mg\/L), Klebsiella pneumoniae (MIC50\/90 0.5\/1\u2005mg\/L), Enterobacter spp. and Citrobacter spp. strains (both MIC50\/90 1\/2\u2005mg\/L). MIC50\/90 values for Proteus mirabilis were &amp;gt;64\/&amp;gt;64\u2005mg\/L. None of ESBL production, meropenem non-WT susceptibility, MDR phenotype or the presence of NDM, KPC, OXA, IMP or VIM carbapenemases impacted on the activity of NOSO-502. In time\u2013kill curves, NOSO-502 showed concentration-dependent killing of E. coli, Klebsiella spp. and C. freundii.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>NOSO-502 showed potent in vitro inhibitory and bactericidal activity against a panel of Enterobacterales enriched for resistant phenotypes for which there are few therapeutic choices. These findings need to be placed in context with the appropriate pharmacokinetic and dynamic characteristics of NOSO-502.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf152","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:13:10Z","timestamp":1747386790000},"page":"1942-1946","source":"Crossref","is-referenced-by-count":1,"title":["<i>In vitro<\/i> activity of NOSO-502, a novel-action antimicrobial, against clinical strains of Enterobacterales including MDR strains"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1047-2098","authenticated-orcid":false,"given":"Marie L G","family":"Attwood","sequence":"first","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), Antimicrobial Reference Laboratory, Infection Sciences, Southmead Hospital , Bristol BS10 5NB ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Noel","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), Antimicrobial Reference Laboratory, Infection Sciences, Southmead Hospital , Bristol BS10 5NB ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pippa","family":"Griffin","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), Antimicrobial Reference Laboratory, Infection Sciences, Southmead Hospital , Bristol BS10 5NB ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilie","family":"Racine","sequence":"additional","affiliation":[{"name":"Nosopharm , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxime","family":"Gualtieri","sequence":"additional","affiliation":[{"name":"Nosopharm , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alasdair","family":"MacGowan","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research and Evaluation (BCARE), Antimicrobial Reference Laboratory, Infection Sciences, Southmead Hospital , Bristol BS10 5NB ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"2025070104564941700_dkaf152-B1","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.3389\/fmicb.2019.02893","article-title":"From worms to drug candidate: the story of odilorhabdins, a new class of antimicrobial agents","volume":"10","author":"Racine","year":"2019","journal-title":"Front Microbiol"},{"key":"2025070104564941700_dkaf152-B2","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.molcel.2018.03.001","article-title":"Odilorhabdins, antibacterial agents that cause miscoding by binding at a new ribosomal site","volume":"70","author":"Pantel","year":"2018","journal-title":"Mol Cell"},{"key":"2025070104564941700_dkaf152-B3","doi-asserted-by":"publisher","first-page":"e01016-18","DOI":"10.1128\/aac.01016-18","article-title":"In vitro and in vivo characterization of NOSO-502, a novel inhibitor of bacterial translation","volume":"62","author":"Racine","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2025070104564941700_dkaf152-B4","doi-asserted-by":"publisher","first-page":"e0077622","DOI":"10.1128\/aac.00776-22","article-title":"Exploring cluster-dependent antibacterial activities and resistance pathways of NOSO-502 and colistin against Enterobacter cloacae complex species","volume":"66","author":"Pantel","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"2025070104564941700_dkaf152-B5","doi-asserted-by":"publisher","first-page":"e01067-18","DOI":"10.1128\/AAC.01067-18","article-title":"In vivo pharmacodynamic characterization of a novel odilorhabdin antibiotic, NOSO-502, against Escherichia coli and Klebsiella pneumoniae in a murine thigh infection model","volume":"62","author":"Zhao","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"author":"ISO","key":"2025070104564941700_dkaf152-B6"},{"key":"2025070104564941700_dkaf152-B7","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1093\/jac\/dkac026","article-title":"Comparative bactericidal activity of representative \u03b2-lactams against Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa","volume":"77","author":"Noel","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2025070104564941700_dkaf152-B8","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1093\/jac\/dkae469","article-title":"Pharmacodynamics of NOSO-502 studied in vitro and in vivo: determination of the dominant pharmacodynamic index driver","volume":"80","author":"van den Berg","year":"2025","journal-title":"J Antimicrobial 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