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Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclea...

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Autores principales: Feng, Jie, Weitner, Megan, Shi, Wanliang, Zhang, Shuo, Sullivan, David, Zhang, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790293/
https://www.ncbi.nlm.nih.gov/pubmed/27025631
http://dx.doi.org/10.3390/antibiotics4030397
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author Feng, Jie
Weitner, Megan
Shi, Wanliang
Zhang, Shuo
Sullivan, David
Zhang, Ying
author_facet Feng, Jie
Weitner, Megan
Shi, Wanliang
Zhang, Shuo
Sullivan, David
Zhang, Ying
author_sort Feng, Jie
collection PubMed
description Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive oxygen species production are more active against the B. burgdorferi persisters than the commonly used antibiotics that inhibit macromolecule biosynthesis. Future studies are needed to evaluate and optimize the promising active hits in drug combination studies in vitro and also in vivo in animal models. These studies may have implications for developing more effective treatments of Lyme disease.
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spelling pubmed-47902932016-03-24 Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library Feng, Jie Weitner, Megan Shi, Wanliang Zhang, Shuo Sullivan, David Zhang, Ying Antibiotics (Basel) Article Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive oxygen species production are more active against the B. burgdorferi persisters than the commonly used antibiotics that inhibit macromolecule biosynthesis. Future studies are needed to evaluate and optimize the promising active hits in drug combination studies in vitro and also in vivo in animal models. These studies may have implications for developing more effective treatments of Lyme disease. MDPI 2015-09-16 /pmc/articles/PMC4790293/ /pubmed/27025631 http://dx.doi.org/10.3390/antibiotics4030397 Text en © 2015 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Feng, Jie
Weitner, Megan
Shi, Wanliang
Zhang, Shuo
Sullivan, David
Zhang, Ying
Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
title Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
title_full Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
title_fullStr Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
title_full_unstemmed Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
title_short Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library
title_sort identification of additional anti-persister activity against borrelia burgdorferi from an fda drug library
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790293/
https://www.ncbi.nlm.nih.gov/pubmed/27025631
http://dx.doi.org/10.3390/antibiotics4030397
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