4.6 Article

Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections

Journal

ANTIBIOTICS-BASEL
Volume 10, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/antibiotics10111372

Keywords

Staphylococcus aureus; MRSA; drug repurposing; eltrombopag; in vivo efficacy

Funding

  1. National Research Foundation of Korea (NRF)
  2. Korean government (MSIT) [NRF-2017M3A9G6068246, 2019M3E5D5064653]
  3. National Research Foundation of Korea [2019M3E5D5064653] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The study screened 182 FDA-approved drugs and identified three potential antibiotic candidates against Staphylococcus aureus. Among them, eltrombopag showed the highest antibacterial activity, with significant potency against not only a drug-sensitive S. aureus strain but also 55 clinical isolates including 35 methicillin-resistant S. aureus.
The continuous rise of antimicrobial resistance urgently demands new therapeutic agents for human health. Drug repurposing is an attractive strategy that could significantly save time delivering new antibiotics to clinics. We screened 182 US Food and Drug Administration (FDA)-approved drugs to identify potential antibiotic candidates against Staphylococcus aureus, a major pathogenic bacterium. This screening revealed the significant antibacterial activity of three small molecule drugs against S. aureus: (1) LDK378 (Ceritinib), an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of lung cancer, (2) dronedarone HCl, an antiarrhythmic drug for the treatment of atrial fibrillation, and (3) eltrombopag, a thrombopoietin receptor agonist for the treatment of thrombocytopenia. Among these, eltrombopag showed the highest potency against not only a drug-sensitive S. aureus strain but also 55 clinical isolates including 35 methicillin-resistant S. aureus (Minimum inhibitory concentration, MIC, to inhibit 50% growth [MIC50] = 1.4-3.2 mg/L). Furthermore, we showed that eltrombopag inhibited bacterial growth in a cell infection model and reduced bacterial loads in infected mice, demonstrating its potential as a new antibiotic agent against S. aureus that can overcome current antibiotic resistance.

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