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 uncle...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-09-01
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| Series: | Antibiotics |
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| Online Access: | http://www.mdpi.com/2079-6382/4/3/397 |
| _version_ | 1818931426970566656 |
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| author | Jie Feng Megan Weitner Wanliang Shi Shuo Zhang David Sullivan Ying Zhang |
| author_facet | Jie Feng Megan Weitner Wanliang Shi Shuo Zhang David Sullivan Ying Zhang |
| author_sort | Jie Feng |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T04:16:25Z |
| format | Article |
| id | doaj.art-2ccd01f4441744d195b7e3397794ead7 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-12-20T04:16:25Z |
| publishDate | 2015-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-2ccd01f4441744d195b7e3397794ead72022-12-21T19:53:46ZengMDPI AGAntibiotics2079-63822015-09-014339741010.3390/antibiotics4030397antibiotics4030397Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug LibraryJie Feng0Megan Weitner1Wanliang Shi2Shuo Zhang3David Sullivan4Ying Zhang5Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USALyme 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.http://www.mdpi.com/2079-6382/4/3/397Borrelia burgdorferipersistersanti-persister activityFDA drug library |
| spellingShingle | Jie Feng Megan Weitner Wanliang Shi Shuo Zhang David Sullivan Ying Zhang Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library Antibiotics Borrelia burgdorferi persisters anti-persister activity 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 | Borrelia burgdorferi persisters anti-persister activity FDA drug library |
| url | http://www.mdpi.com/2079-6382/4/3/397 |
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