ArticlePLoS pathogens2025
Bacterial and host enzymes modulate the pro-inflammatory response elicited by the peptidoglycan of Lyme disease agent Borrelia burgdorferi.
Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- A cofactor-promiscuous HMGR from the Lyme disease pathogen illuminates diversity in bacterial isoprenoid biosynthesis.Protein science : a publication of the Protein Society · 2026Article
- Review
- Bactofilins are essential spatial organizers of peptidoglycan insertion in the Lyme disease spirocheteJournal of bacteriology · 2026Article
- A cofactor-promiscuous HMGR from the Lyme disease pathogen illuminates diversity in bacterial isoprenoid biosynthesis.bioRxiv : the preprint server for biology · 2026Article
- Characterization ofMicroorganisms · 2026Article
- Peptidoglycan architecture dictates protein interactions, tissue tropism, and arthritis in the Lyme disease spirochete Borrelia burgdorferi.PLoS pathogens · 2026Article
- From forest floor to doctor's office: the immunological journey ofFrontiers in immunology · 2026Review
- Aspects of the Immunopathogenesis of Lyme Arthritis.Microorganisms · 2025Review
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Abstract
The spirochete Borrelia burgdorferi causes Lyme disease. In some patients, an excessive, dysregulated proinflammatory immune response can develop in joints leading to persistent arthritis even after antibiotic therapy. In such patients, persistence of antigenic B. burgdorferi peptidoglycan (PGBb) fragments within joint tissues may contribute to immunopathogenesis pre- and post-antibiotic treatment. In live B. burgdorferi cells, the outer membrane shields the polymeric PGBb sacculus from exposure to the immune system. However, unlike most diderm bacteria, B. burgdorferi releases PGBb turnover products into its environment due to the absence of recycling activity. In this study, we identified the released PGBb fragments using a mass spectrometry-based approach. By characterizing the l,d-carboxypeptidase activity of B. burgdorferi protein BB0605 (renamed DacA), we found that PGBb turnover largely occurs at sites of PGBb synthesis. In parallel, we demonstrated that the lytic transglycosylase activity associated with BB0259 (renamed MltS) releases PGBb fragments with 1,6-anhydro bond on their N-acetylmuramyl residues. Stimulation of human cell lines with various synthetic PGBb fragments revealed that 1,6-anhydromuramyl-containing PGBb fragments are poor inducers of a NOD2-dependent immune response relative to their hydrated counterparts found in the polymeric PGBb isolated from dead bacteria. We also showed that the activity of the human N-acetylmuramyl-l-alanine amidase PGLYRP2, which reduces the immunogenicity of PGBb material, is low in joint (synovial) fluids relative to serum. Altogether, our findings suggest that MltS activity helps B. burgdorferi evade PG-based immune detection by NOD2 during growth despite shedding PGBb fragments and that PGBb-induced immunopathology likely results from host sensing of PGBb material from dead (lysed) spirochetes. Additionally, our results suggest the possibility that natural variation in PGLYRP2 activity may contribute to differences in susceptibility to PG-induced inflammation across tissues and individuals.
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