{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:58:39Z","timestamp":1774382319397,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI083214"],"award-info":[{"award-number":["AI083214"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean government","award":["2020R1C1C1008842, 2018R1A5A2025286 and 2017M3A9E4077234"],"award-info":[{"award-number":["2020R1C1C1008842, 2018R1A5A2025286 and 2017M3A9E4077234"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Multidrug-resistant pathogens pose a serious threat to human health. For decades, the antibiotic vancomycin has been a potent option when treating Gram-positive multidrug-resistant infections. Nonetheless, in recent decades, we have begun to see an increase in vancomycin-resistant bacteria. Here, we show that the nuclear factor-kappa B (NF-\u03baB) inhibitor N-[3,5-Bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (IMD0354) was identified as a positive hit through a Caenorhabditis elegans\u2013methicillin-resistant Staphylococcus aureus (MRSA) infection screen. IMD0354 was a potent bacteriostatic drug capable of working at a minimal inhibitory concentration (MIC) as low as 0.06 \u00b5g\/mL against various vancomycin-resistant strains. Interestingly, IMD0354 showed no hemolytic activity at concentrations as high as 16 \u00b5g\/mL and is minimally toxic to C. elegans in vivo with 90% survival up to 64 \u00b5g\/mL. In addition, we demonstrated that IMD0354\u2032s mechanism of action at high concentrations is membrane permeabilization. Lastly, we found that IMD0354 is able to inhibit vancomycin-resistant Staphylococcus aureus (VRSA) initial cell attachment and biofilm formation at sub-MIC levels and above. Our work highlights that the NF-\u03baB inhibitor IMD0354 has promising potential as a lead compound and an antimicrobial therapeutic candidate capable of combating multidrug-resistant bacteria.<\/jats:p>","DOI":"10.3390\/antibiotics9100665","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T11:28:57Z","timestamp":1601551737000},"page":"665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["New Antimicrobial Bioactivity against Multidrug-Resistant Gram-Positive Bacteria of Kinase Inhibitor IMD0354"],"prefix":"10.3390","volume":"9","author":[{"given":"Iliana E","family":"Escobar","sequence":"first","affiliation":[{"name":"Infectious Diseases Division, Department of Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"White","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Department of Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wooseong","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleftherios","family":"Mylonakis","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Department of Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1128\/CMR.00081-09","article-title":"Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic","volume":"23","author":"David","year":"2010","journal-title":"Clin. 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