Lyme disease is a tickborne illness caused by the bacterium Borrelia burgdorferi which is transmissible to humans through the bite of infected blacklegged ticks. In the United States, more than 300,000 cases of Lyme Disease are diagnosed yearly, and this number has been steadily increasing over the past 25 years. The majority of cases are successfully treated with oral antibiotics; however, some patients experience symptoms after treatment, referred to as post-treatment Lyme disease syndrome (PTLDS). Better therapeutic options could decrease the incidence of PTLDS. We developed a screen for compounds acting selectively against B. burgdorferi. Screening of extracts from soil bacteria led us to rediscover hygromycin A. This antibiotic was originally discovered in 1953 Streptomyces hygroscopicus by Selman Waksman and his colleagues. The compound had low activity against typical pathogens and was not pursued. Hygromycin A S. aureus MIC is 32 µg/mL E. coli MIC is 1,000 µg/mL. By contrast, B. burgdorferi MIC is 0.12 µg/mL – it is 250-fold more active against this pathogen as compared to S. aureus. Hygromycin A delivered subcutaneously cleared B. burgdorferi in a mouse model of Lyme disease. Importantly, orally administered hygromycin A was similarly effective in treating the infection. Currently used antibiotics to treat Lyme disease have been borrowed from other applications. Hygromycin A holds the promise of providing superior, and selective, treatment of Lyme disease.

Hygromycin A, an antimicrobial with selective activity against Borrelia burgdorferi for treatment of Lyme disease

256th National Meeting (2018)

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