Abstract
Lyme disease is the leading tick-borne disease in the USA. Whereas the majority of Lyme disease patients with early disease can be cured with standard treatment, some patients suffer from chronic fatigue and joint and muscular pain despite treatment, a syndrome called posttreatment Lyme disease syndrome. Although the cause is unclear, ineffective killing of Borrelia burgdorferi persisters by current Lyme disease antibiotics is one possible explanation. We took advantage of our recently developed high-throughput viability assay and screened the National Cancer Institute compound library collection consisting of 2526 compounds against stationary phase B. burgdorferi. We identified the top 30 new active hits, including the top six anthracycline antibiotics daunomycin 3-oxime, dimethyldaunomycin, daunomycin, NSC299187, NSC363998 and nogalamycin, along with other compounds, including prodigiosin, mitomycin, nanaomycin and dactinomycin, as having excellent activity against B. burgdorferi stationary phase culture. The anthracycline or anthraquinone compounds, which are known to have both anti-cancer and antibacterial activities, also had high activity against growing B. burgdorferi with low minimum inhibitory concentration. Future studies on the structure–activity relationship and mechanisms of action of anthracyclines/anthraquinones are warranted. In addition, drug combination studies with the anthracycline class of compounds and the current Lyme antibiotics to eradicate B. burgdorferi persisters in vitro and in animal models are needed to determine if they improve the treatment of Lyme disease.
Highlights
Lyme disease is a multisystem disease caused by the spirochetal bacterium Borrelia burgdorferi and is the leading tick-borne disease in the USA.1 The clinical manifestations of Lyme disease are characterized by an erythema migrans rash and an influenza-like illness, with arthritis and neurological disorders as frequent sequelae of the disease
The findings indicate the continued presence of B. burgdorferi in some form and suggest that current Lyme treatment may not be sufficient to eliminate B. burgdorferi persisters or that the immune system fails to clear persisting organisms or bacterial debris, which may be underlying causes for those who suffer from nonresolving symptoms of Lyme disease
Based on our previous study that demonstrated the antibiotic tolerance of the stationary phase cultures,12 we chose seven-day-old stationary phase B. burgdorferi cultures (1 3 107 spirochetes/mL) enriched in persisters for drug screens in 96-well microtiter plates, as previously described
Summary
Lyme disease is a multisystem disease caused by the spirochetal bacterium Borrelia burgdorferi and is the leading tick-borne disease in the USA. The clinical manifestations of Lyme disease are characterized by an erythema migrans rash and an influenza-like illness, with arthritis and neurological disorders as frequent sequelae of the disease. Lyme disease is a multisystem disease caused by the spirochetal bacterium Borrelia burgdorferi and is the leading tick-borne disease in the USA.. The question of whether B. burgdorferi might persist in some patients after antibiotic therapy and further evade host immune clearance has been raised by some, but it is controversial. The findings indicate the continued presence of B. burgdorferi in some form and suggest that current Lyme treatment may not be sufficient to eliminate B. burgdorferi persisters or that the immune system fails to clear persisting organisms or bacterial debris, which may be underlying causes for those who suffer from nonresolving symptoms of Lyme disease. There is currently no effective antibiotic treatment or preventative strategy for those who suffer from persistent symptoms after Lyme disease
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