DRUG COMBINATIONS FOR BORRELIA PERSISTERS
A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library Jie Feng1, Wanliang Shi1, Shuo Zhang1, David Sullivan1, Paul Auwaerter2 and Ying Zhang1* 1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, USA 2Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, USA Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA) drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI) viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. While some drug candidates such as daptomycin and clofazimine overlapped with a previous screen against stationary phase B. burgdorferi persisters, additional drug candidates active against round bodies we identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had...Lyme in the 21st Century
Published on Apr 20, 2016 Ten of the world’s top scientists from leading institutions discuss their scientific insights on the problems and potential solutions for Lyme disease. Notes from the video – Senator Richard Blumenthall US Senate Speech ‘The cases of Lyme are exploding in number and their severity impacts our economy as well as quality of life for Americans’ Introduced by David Rothman– Lyme Advocate CDC reported 10 fold increase in the number of cases in 2013. Dr Neil Spector Cancer researcher talks about implications in organ donation. He had a heart transplant due to undiagnosed Lyme Disease. ‘In the era of genomics are we using archaic unreliable methods to test for Lyme?’ Dr William H Robinson Stanford University talks about the need to develop next generation tests that are much more accurate and sensitive to identify people with Borrelia Burgdorferi as well as other tick borne infections. Dr Safwan Jaradeh Stanford University Neuromuscular and Neurological faculty. ‘Nobody seems to think well could it be something like Lyme.’ Dr Brian Fallon Columbia University Director of the Lyme and Tick-borne diseases research center at Columbia. says – Lyme can cause many symptoms he talks about a child who manifested with compulsive cycling behaviour and anorexia which was caused by Lyme Disease and with treatment symptoms went away. Dr Neil Spector goes on to say- ‘Over 300000 cases a year I think demands more attention than Zika virus which overnight becomes a W.H.O. global health crisis. So it’s not to minimize the problems of Zika but it is saying there are...
