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 antimicrobiota 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 antimicrobiota 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.

Animal Biotechnology Department Center for Genetic Engineering and Biotechnology Avenue 31 between 158 and 190 PO Box 6162 Havana 10600 Cuba

ANSES INRAE Ecole Nationale Vétérinaire d'Alfort UMR BIPAR Laboratoire de Santé Animale Maisons Alfort F 94700 France

Centre Algatech Institute of Microbiology Czech Academy of Sciences Novohradská 237 Třeboň 37901 Czech Republic

Direction of Animal Health National Center for Animal and Plant Health Carretera de Tapaste y Autopista Nacional Apartado Postal 10 32700 San José de las Lajas Mayabeque Cuba

Faculty of Science University of South Bohemia Ceske Budejovice Czech Republic

Institute of Parasitology Biology Centre Czech Academdiseases by targeting metabolite pathways y of Sciences Ceske Budejovice Czech Republic

Laboratoire de Chimie Moléculaire UMR 9168 CNRS Ecole Polytechnique Route de Saclay Palaiseau 91120 France

Laboratory of Analytical Biochemistry and Metabolomics Biology Centre Czech Academy of Sciences České Budějovice 37005 Czech Republic

Laboratory of Microbiology National School of Veterinary Medicine of Sidi Thabet University of Manouba Manouba 2010 Tunisia

School of Environmental Sciences University of Guelph Guelph ON N1H 2W1 Canada

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