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...Cancer Researcher Who Nearly Died of Lyme Discusses the Similarities Between the Two Diseases
Neil Spector, MD, author of Gone in a Heartbeat: A Physician’s Search for True Healing spoke at the International Lyme and Associated Diseases Society (ILADS) annual conference. FT. LAUDERDALE, FL., October 15, 2015– Neil Spector, MD knows cancer. As a leading researcher, he led the development of two targeted cancer therapies which were FDA approved. He is currently the Sandra Coates Chair in Breast Cancer Research at Duke University. But in 2009, Dr. Spector faced his own mortality when a physician informed him he would die without a heart transplant. Dr. Spector’s heart had been destroyed by an undiagnosed case of Lyme disease. Dr. Spector discussed his experiences as an oncologist and Lyme disease survivor on Friday, October 16, 2015 at the ILADS conference held at the Marriott Harbor Beach Resort in Fr. Lauderdale, Florida. His presentation was titled: How Lessons from Personalized Cancer Care Can Inform Management of Lyme Disease. Dr. Spector calls Lyme disease “the infectious disease equivalent of cancer.” Cancer is not one specific disease and neither is Lyme, says Spector. “We talk about Lyme Disease as if it is ONE disease caused by one uniform strain of Borrelia when we know there are at least 16 pathogenic strains of the bacteria that cause disease in the United States.” Spector notes both cancer cells and Borrelia burdoferi (the spirochete which causes Lyme disease) are equipped with mechanisms to resist therapeutic interventions. Both pathogens have a “sweet tooth,” says Spector, since each relies on glucose as a source of energy. Yet, while cancer specialists design personalized treatment plans for cancer patients, Lyme disease treatments are...Prof Kim Lewis – Persister Borrelia
The Paradox of Chronic Infections – Kim Lewis What processes take place in a bacteria population under antibiotic treatment? What important discovery made during World War II was forgotten? How can we circumvent the protection mechanisms used by bacteria populations? Professor of Biology at Northeastern University Kim Lewis explains the significance of a rediscovered phenomenon. Northeastern University researchers have found that the bacterium that causes Lyme disease forms dormant persister cells, which are known to evade antibiotics. This significant finding, they said, could help explain why it’s so difficult to treat the infection in some patients. Researchers’ discovery may explain difficulty in treating Lyme disease – “This is the first time, we think, that pulse-dosing has been published as a method for eradicating the population of a pathogen with antibiotics that don’t kill dormant cells,” Lewis said. “The trick to doing this is to allow the dormant cells to wake up.” He added: “This gives you an idea that you could, in principle, establish a similar regiment for treating patients for this and other chronic diseases.” http://www.northeastern.edu/news/2015/06/researchers-discovery-may-explain-difficulty-in-treating-lyme-disease/ Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Bijaya Sharma, Autumn V. Brown, Nicole E. Matluck, Linden T. Hu and Kim Lewis —————————————————– Other videos of Prof Lewis Principles of Antibiotic Discovery – Kim Lewis https://www.youtube.com/watch?v=89MdHzNHGZI&list=UUComKOHir2WrDuRZXP8DT-A Uncultured Bacteria – Kim Lewis https://www.youtube.com/watch?v=-ojRvlwanSA What lights my fire https://www.youtube.com/watch?v=GBZ9hyrMsoM Prof Lewis team at Northeastern were recently in the news for their discovery of a new antibiotic Teixobactin http://www.ncbi.nlm.nih.gov/pubmed/25561178 Prof Lewis featured in a BBC documentary on Panorama on his research into finding new antibiotics http://www.bbc.co.uk/news/health-32701896 and earlier http://www.bbc.co.uk/news/health-30657486 ...
