Dataset Information

Persister Development by Borrelia burgdorferi Populations In Vitro.

ABSTRACT: Doxycycline is an antibiotic commonly used to treat Lyme disease and other bacterial infections. The MIC and minimum bactericidal concentration (MBC) for Borrelia burgdorferi have been investigated by different groups but were experimentally established in this study as a function of input cell density. We demonstrated that B. burgdorferi treated in the stationary phase has a higher probability of regrowth following removal of antibiotic. In addition, we determined experimentally and mathematically that the spirochetes which persist posttreatment do not have a longer lag phase but exhibit a lower growth rate than untreated spirochetes. Finally, we found that treating the spirochetes by pulse-dosing did not eliminate growth or reduce the persister population in vitro. From these data, we propose that B. burgdorferi persister development is stochastic and driven by slowed growth.

SUBMITTER: Caskey JR

PROVIDER: S-EPMC4576077 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Persister Development by Borrelia burgdorferi Populations In Vitro.

Caskey John R JR Embers Monica E ME

Antimicrobial agents and chemotherapy 20150727 10

Doxycycline is an antibiotic commonly used to treat Lyme disease and other bacterial infections. The MIC and minimum bactericidal concentration (MBC) for Borrelia burgdorferi have been investigated by different groups but were experimentally established in this study as a function of input cell density. We demonstrated that B. burgdorferi treated in the stationary phase has a higher probability of regrowth following removal of antibiotic. In addition, we determined experimentally and mathematica ...[more]

PMID: 26248368

Similar Datasets

Project 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/?-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.

Dataset Information

Persister Development by Borrelia burgdorferi Populations In Vitro.

Publications

Persister Development by Borrelia burgdorferi Populations In Vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets