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Screening of an FDA-Approved Library for Novel Drugs against Y. pestis

Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is...

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Detalles Bibliográficos
Autores principales: Gur, David, Chitlaru, Theodor, Mamroud, Emanuelle, Zauberman, Ayelet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823876/
https://www.ncbi.nlm.nih.gov/pubmed/33401634
http://dx.doi.org/10.3390/antibiotics10010040
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author Gur, David
Chitlaru, Theodor
Mamroud, Emanuelle
Zauberman, Ayelet
author_facet Gur, David
Chitlaru, Theodor
Mamroud, Emanuelle
Zauberman, Ayelet
author_sort Gur, David
collection PubMed
description Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset. To overcome the emergence of antibiotic resistant strains, we attempted a systematic screening of Food and Drug Administration (FDA)-approved drugs to identify alternative compounds which may possess antibacterial activity against Y. pestis. Here, we describe a drug-repurposing approach, which led to the identification of two antibiotic-like activities of the anticancer drugs bleomycin sulfate and streptozocin that have the potential for designing novel antiplague therapy approaches. The inhibitory characteristics of these two drugs were further addressed as well as their efficiency in affecting the growth of Y. pestis strains resistant to doxycycline and ciprofloxacin, antibiotics recommended for plague treatment.
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spelling pubmed-78238762021-01-24 Screening of an FDA-Approved Library for Novel Drugs against Y. pestis Gur, David Chitlaru, Theodor Mamroud, Emanuelle Zauberman, Ayelet Antibiotics (Basel) Article Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset. To overcome the emergence of antibiotic resistant strains, we attempted a systematic screening of Food and Drug Administration (FDA)-approved drugs to identify alternative compounds which may possess antibacterial activity against Y. pestis. Here, we describe a drug-repurposing approach, which led to the identification of two antibiotic-like activities of the anticancer drugs bleomycin sulfate and streptozocin that have the potential for designing novel antiplague therapy approaches. The inhibitory characteristics of these two drugs were further addressed as well as their efficiency in affecting the growth of Y. pestis strains resistant to doxycycline and ciprofloxacin, antibiotics recommended for plague treatment. MDPI 2021-01-03 /pmc/articles/PMC7823876/ /pubmed/33401634 http://dx.doi.org/10.3390/antibiotics10010040 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gur, David
Chitlaru, Theodor
Mamroud, Emanuelle
Zauberman, Ayelet
Screening of an FDA-Approved Library for Novel Drugs against Y. pestis
title Screening of an FDA-Approved Library for Novel Drugs against Y. pestis
title_full Screening of an FDA-Approved Library for Novel Drugs against Y. pestis
title_fullStr Screening of an FDA-Approved Library for Novel Drugs against Y. pestis
title_full_unstemmed Screening of an FDA-Approved Library for Novel Drugs against Y. pestis
title_short Screening of an FDA-Approved Library for Novel Drugs against Y. pestis
title_sort screening of an fda-approved library for novel drugs against y. pestis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823876/
https://www.ncbi.nlm.nih.gov/pubmed/33401634
http://dx.doi.org/10.3390/antibiotics10010040
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