Borrelia burgdorferi response to Antibiotic Treatment

With an estimated 300,000 new cases annually, Lyme disease is the most common vector-borne disease in North America. The causative agent, Borrelia burgdorferi (Bb) is a spirochete that can chronically infect humans, causing rash, arthritis, carditis, myalgia, extreme fatigue and neurological dysfunction. Despite generally effective treatment with antibiotics, a proportion of Lyme disease patients continue to experience symptoms after antibiotic treatment, a phenomenon that can be labeled as Post-treatment Lyme Disease Syndrome (PTLDS). The efficacy and accepted regimen of antibiotic treatment for human Borreliosis has been a very contentious issue. We have shown that Bb spirochetes can persist following a standard antibiotic treatment of disseminated infection in nonhuman primates (NHP).  We now aim to understand how Bb can persist in the presence of doxycycline-the most commonly-prescribed antibiotic for Lyme disease. We have examined doxycycline efficacy in vitro as a function of bacterial growth phase and performed pulse-dose experiments to explore persister development. Finally, RNA sequencing was performed on treated cultures to identify genes associated with persister development.  Our results indicate that persister development is much more probable with treatment of stationary phase cultures and their development is stochastic.  We have also identified a number of metabolic genes and virulence determinants that may be involved in persister development.  These findings could help guide the assessment of candidate antibiotic treatment regimens for Lyme disease.