New antimicrobial bioactivity against multidrugresistant gram-positive bacteria of kinase inhibitor imd0354
- 주제(키워드) High-throughput screening , IMD0354 , Vancomycin-resistant Staphylococcus aureus , Vancomycinresistant enterococci
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI AG
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174806
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/antibiotics9100665
- PubMed https://pubmed.ncbi.nlm.nih.gov/33019726
초록/요약
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-κB) inhibitor N-[3,5Bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (IMD0354) was identified as a positive hit through a Caenorhabditis elegans–methicillin-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 µg/mL against various vancomycin-resistant strains. Interestingly, IMD0354 showed no hemolytic activity at concentrations as high as 16 µg/mL and is minimally toxic to C. elegans in vivo with 90% survival up to 64 µg/mL. In addition, we demonstrated that IMD0354′s 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-κB inhibitor IMD0354 has promising potential as a lead compound and an antimicrobial therapeutic candidate capable of combating multidrug-resistant bacteria. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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