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Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections

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 ident...

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Autores principales: Lee, Hyunjung, Lee, Jaehoan, Hwang, Juchan, Park, Sinyoung, Kim, Namyoul, Kim, Kideok, Lee, Honggun, Shum, David, Jang, Soojin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615030/
https://www.ncbi.nlm.nih.gov/pubmed/34827309
http://dx.doi.org/10.3390/antibiotics10111372
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author Lee, Hyunjung
Lee, Jaehoan
Hwang, Juchan
Park, Sinyoung
Kim, Namyoul
Kim, Kideok
Lee, Honggun
Shum, David
Jang, Soojin
author_facet Lee, Hyunjung
Lee, Jaehoan
Hwang, Juchan
Park, Sinyoung
Kim, Namyoul
Kim, Kideok
Lee, Honggun
Shum, David
Jang, Soojin
author_sort Lee, Hyunjung
collection PubMed
description 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 [MIC(50)] = 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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spelling pubmed-86150302021-11-26 Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections Lee, Hyunjung Lee, Jaehoan Hwang, Juchan Park, Sinyoung Kim, Namyoul Kim, Kideok Lee, Honggun Shum, David Jang, Soojin Antibiotics (Basel) Article 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 [MIC(50)] = 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. MDPI 2021-11-09 /pmc/articles/PMC8615030/ /pubmed/34827309 http://dx.doi.org/10.3390/antibiotics10111372 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Hyunjung
Lee, Jaehoan
Hwang, Juchan
Park, Sinyoung
Kim, Namyoul
Kim, Kideok
Lee, Honggun
Shum, David
Jang, Soojin
Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections
title Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections
title_full Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections
title_fullStr Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections
title_full_unstemmed Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections
title_short Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections
title_sort repurposing eltrombopag for multidrug resistant staphylococcus aureus infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615030/
https://www.ncbi.nlm.nih.gov/pubmed/34827309
http://dx.doi.org/10.3390/antibiotics10111372
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