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

Case ID:
C13754
Disclosure Date:
7/28/2015
Description:
Lyme disease is a leading vector borne disease in the US. 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 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 glutathione/?-glutamyl pathway involved in protection against free radical damage, and also 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 treatment of Lyme disease.
Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library PCT: Patent Cooperation Treaty PCT PCT/US2016/047784   8/19/2016     Expired
Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library PCT: Patent Cooperation Treaty United States 15/754,191 2/21/2018     Pending
Inventors:
Category(s):
For Information, Contact:
Sonriza Ford
sford23@jhu.edu
410-614-0300
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