Anti-microbiota vaccine induces lysine-mediated modulation of tick immunity affecting Borrelia colonization.

Tick microbiota influences Borrelia colonization, but changes in the microbiota-derived metabolite and how this affects tick physiology and vector competence is unclear. We investigated whether microbiota-induced metabolite modifications influence tick physiology and pathogen transmission. Using an anti-microbiota vaccine (live Escherichia coli) to immunize mice, we generated host antibodies that modulated the tick microbiome, decreasing bacterial abundance and increasing lysine levels in ticks. Elevated lysine correlated with increased tick weight. Lysine supplementation experiments enhanced defensin expression with DefMT6 exhibiting anti-Borrelia activity, reducing pathogen load in ticks. Our findings demonstrate that anti-microbiota vaccines induce metabolite changes, affecting tick physiology, immunity, and vector competence. These insights open new avenues for developing microbiota-targeted strategies to control tick-borne diseases.