New antimicrobial bioactivity against multidrugresistant gram-positive bacteria of kinase inhibitor imd0354

Iliana E. Escobar, Alexis White, Wooseong Kim, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish
Article number665
Pages (from-to)1-17
Number of pages17
Issue number10
StatePublished - Oct 2020

Bibliographical note

Funding Information:
Funding: This research was funded by NIH grant P01 AI083214 to E.M. W.K. is supported by the National Research Foundation of Korea Grants funded by the Korea government (MSIT) (2020R1C1C1008842, 2018R1A5A2025286 and 2017M3A9E4077234). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript, apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • High-throughput screening
  • IMD0354
  • Vancomycin-resistant Staphylococcus aureus
  • Vancomycinresistant enterococci


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