DRUG COMBINATIONS FOR BORRELIA PERSISTERS

May 12, 2016 | Uncategorised

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...

Prof Ying Zhang Borrelia persisters – Interview and drug activity

Nov 17, 2015 | Uncategorised

  Interview with Prof. Ying Zhang at the NorVect Conference 2015 Published on Sep 29, 2015 Prof Ying Zhang from John Hopkins Bloomberg School of Public Health explains why Lyme disease is so difficult to treat. Having worked with Tuberculosis (TB) for many years, he sees the similarities and differences between these to bacteria. With Tuberculosis it is known that you have to treat with certain drug combinations that kill the growing form and the non-growing form (persisters) and if you treat shorter than 6 months, the patient will get a relapse. The bacterium that causes Lyme disease is much more advanced than the TB bacterium, and the main reason is that it also takes a persisting form. These persister forms of the Borrelia bacteria cannot be cultured. The two views – ILADS and IDSA are two different ways of seeing the same disease. Prof. Zhang thinks they are both right. When it comes to acute Lyme disease, IDSA is right. Then you only need shorter courses of treatment. When the disease turns chronic, longer courses of treatment with the right drug combinations are needed (ILADS view). The full presentation from Dr Zhang is available on the Norvect website from their 2015 conference http://norvect.no/about-norvect/     Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library Jie Feng, Ting Wang, Wanliang Shi, Shuo Zhang, David Sullivan, Paul G Auwaerter and Ying Zhang Published online 2 July 2014 from abstract – ‘We identified 165 agents approved for use in other disease conditions that had more activity than doxycycline and amoxicillin against B. burgdorferi persisters. The top 27 drug candidates from the 165 hits were confirmed to have higher anti-persister activity than the current frontline antibiotics....