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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8615030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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