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.

• Keywords
• Borrelia, defensins, lysine, metabolites, tick immunity, tick microbiota, tick physiology, vector competence,
• MeSH
• Bacterial Vaccines * immunology   MeSH
• Borrelia burgdorferi * immunology   MeSH
• Borrelia * immunology   MeSH
• Escherichia coli immunology   MeSH
• Ixodes * microbiology   immunology   MeSH
• Lyme Disease prevention & control   immunology   MeSH
• Lysine * metabolism   MeSH
• Microbiota MeSH
• Mice MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bacterial Vaccines * MeSH
• Lysine * MeSH

Pathogenic spirochetes bind and interact with various host structures and molecules throughout the course of infection. By utilizing their outer surface molecules, spirochetes can effectively modulate their dissemination, interact with immune system regulators, and select specific destination niches within the host. The three-dimensional structures of multiple spirochetal surface proteins have been elucidated, providing insight into their modus operandi. This review focuses on the structural characteristics of these sticky molecules and their functional implications, highlighting how these features contribute to the pathogenicity of spirochetes and their ability to persist in the host and vector environments. Recognizing the structural motifs and ligands to which these important virulence determinants bind could open new avenues for developing strategies to block colonization by spirochetal pathogens.

• Keywords
• Borrelia, Leptospira, Treponema, adhesins, atomic structure, infection, lipoproteins, nuclear magnetic resonance, spirochetes, x‐ray crystallography,
• MeSH
• Bacterial Proteins chemistry   MeSH
• Host Microbial Interactions * MeSH
• Humans MeSH
• Ligands MeSH
• Membrane Proteins chemistry   MeSH
• Spirochaetales * chemistry   MeSH
• Spirochaetales Infections * microbiology   MeSH
• Protein Structure, Tertiary MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Bacterial Proteins MeSH
• Ligands MeSH
• Membrane Proteins MeSH