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Genetic background amplifies the effect of immunodeficiency in antibiotic efficacy against Borrelia burgdorferi.

Unrecognized immunodeficiency has been proposed as a possible cause of failure of antibiotics to resolve symptoms of Lyme disease. Here, we examined the efficacy of doxycycline in different immune deficient mice to identify defects that impair antibiotic treatment outcomes. We found that doxycycline had significantly lower efficacy in the absence of adaptive immunity, specifically B cells. This effect was most pronounced in immunodeficientC3H mice compared with C57BL/6 mice suggesting a role for genetic background beyond immunodeficiency. Addition of a single dose of ceftriaxone to doxycycline treatment effectively cleared infection in C3H mice with severe combined immunodeficiency.