Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> 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:	Hyunjung Lee, Jaehoan Lee, Juchan Hwang, Sinyoung Park, Namyoul Kim, Kideok Kim, Honggun Lee, David Shum, Soojin Jang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Staphylococcus aureus</i> MRSA drug repurposing eltrombopag in vivo efficacy Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/54499e74f7e9429e8cf4f4580150980d
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spelling	oai:doaj.org-article:54499e74f7e9429e8cf4f4580150980d2021-11-25T16:24:03ZRepurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections10.3390/antibiotics101113722079-6382https://doaj.org/article/54499e74f7e9429e8cf4f4580150980d2021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1372https://doaj.org/toc/2079-6382The 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 <i>Staphylococcus aureus</i>, a major pathogenic bacterium. This screening revealed the significant antibacterial activity of three small molecule drugs against <i>S. aureus</i>: (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 <i>S. aureus</i> strain but also 55 clinical isolates including 35 methicillin-resistant <i>S. aureus</i> (Minimum inhibitory concentration, MIC, to inhibit 50% growth [MIC<sub>50</sub>] = 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 <i>S. aureus</i> that can overcome current antibiotic resistance.Hyunjung LeeJaehoan LeeJuchan HwangSinyoung ParkNamyoul KimKideok KimHonggun LeeDavid ShumSoojin JangMDPI AGarticle<i>Staphylococcus aureus</i>MRSAdrug repurposingeltrombopagin vivo efficacyTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1372, p 1372 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Staphylococcus aureus</i> MRSA drug repurposing eltrombopag in vivo efficacy Therapeutics. Pharmacology RM1-950
spellingShingle	<i>Staphylococcus aureus</i> MRSA drug repurposing eltrombopag in vivo efficacy Therapeutics. Pharmacology RM1-950 Hyunjung Lee Jaehoan Lee Juchan Hwang Sinyoung Park Namyoul Kim Kideok Kim Honggun Lee David Shum Soojin Jang Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections
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 <i>Staphylococcus aureus</i>, a major pathogenic bacterium. This screening revealed the significant antibacterial activity of three small molecule drugs against <i>S. aureus</i>: (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 <i>S. aureus</i> strain but also 55 clinical isolates including 35 methicillin-resistant <i>S. aureus</i> (Minimum inhibitory concentration, MIC, to inhibit 50% growth [MIC<sub>50</sub>] = 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 <i>S. aureus</i> that can overcome current antibiotic resistance.
format	article
author	Hyunjung Lee Jaehoan Lee Juchan Hwang Sinyoung Park Namyoul Kim Kideok Kim Honggun Lee David Shum Soojin Jang
author_facet	Hyunjung Lee Jaehoan Lee Juchan Hwang Sinyoung Park Namyoul Kim Kideok Kim Honggun Lee David Shum Soojin Jang
author_sort	Hyunjung Lee
title	Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections
title_short	Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections
title_full	Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections
title_fullStr	Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections
title_full_unstemmed	Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections
title_sort	repurposing eltrombopag for multidrug resistant <i>staphylococcus aureus</i> infections
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/54499e74f7e9429e8cf4f4580150980d
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Repurposing Eltrombopag for Multidrug Resistant <i>Staphylococcus aureus</i> Infections

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