Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections.
Hyunjung LeeJaehoan LeeJuchan HwangSinyoung ParkNamyoul KimKideok KimHonggun LeeDavid ShumSoojin JangPublished in: Antibiotics (Basel, Switzerland) (2021)
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.
Keyphrases
- staphylococcus aureus
- human health
- small molecule
- multidrug resistant
- antimicrobial resistance
- risk assessment
- atrial fibrillation
- drug administration
- primary care
- heart failure
- drug resistant
- single cell
- type diabetes
- adipose tissue
- climate change
- escherichia coli
- cell therapy
- cystic fibrosis
- combination therapy
- mesenchymal stem cells
- metabolic syndrome
- methicillin resistant staphylococcus aureus
- klebsiella pneumoniae
- venous thromboembolism
- insulin resistance
- catheter ablation
- direct oral anticoagulants
- silver nanoparticles
- high fat diet induced
- recombinant human