fmicb-07-00743 May 20, 2016 Time: 19:28 # 1 ORIGINAL RESEARCH published: 23 May 2016 doi: 10.3389/fmicb.2016.00743 A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library Jie Feng1, Wanliang Shi1, Shuo Zhang1, David Sullivan1, Paul G. Auwaerter2 and Ying Zhang1* 1 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA, 2 Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, 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 Edited by: Octavio Luiz Franco, for Lyme disease may experience lingering symptoms including fatigue, pain, or Universidade Católica de Brasília, joint and muscle aches. Under experimental stress conditions such as starvation Brazil or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which Reviewed by: are a type of persister bacteria that appear resistant in vitro to customary first-line Tom Coenye, Ghent University, antibiotics for Lyme disease. To identify more effective drugs with activity against the Belgium round body form of B. burgdorferi, we established a round body persister model Elizabete De Souza Cândido, Catholic University Dom Bosco, induced by exposure to amoxicillin (50 mg/ml) and then screened the Food and Brazil Drug Administration drug library consisting of 1581 drug compounds and also 22 *Correspondence: drug combinations using the SYBR Green I/propidium iodide viability assay. We Ying Zhang identified 23 drug candidates that have higher activity against the round bodies of
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