Synthesis of a Borrelia burgdorferi -Derived Muropeptide Standard Fragment Library

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 14; p. 3297
• Main Authors: Putnik, Rachel, Zhou, Junhui, Irnov, Irnov, Garner, Elise, Liu, Min, Bersch, Klare L, Jacobs-Wagner, Christine, Grimes, Catherine Leimkuhler
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.07.2024
• Subjects: Amino acids; Antibiotics; Arthritis; Bacteria; Borrelia burgdorferi - immunology; Cell Wall - chemistry; glycosylation; Gram-negative bacteria; Gram-positive bacteria; Humans; Hydrogenation; Immune system; Immunology; Infections; innate immunity; Libraries; Lyme disease; Lyme Disease - drug therapy; Lyme Disease - immunology; Lyme Disease - microbiology; ornithine; Pathogens; peptide coupling; Peptides; peptidoglycan (PG); Peptidoglycan - chemistry; Peptidoglycan - immunology; Recycling; United States > US; Lyme disease; ornithine; glycosylation; peptide coupling; innate immunity; peptidoglycan (PG)
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29143297

The interplay between the human innate immune system and bacterial cell wall components is pivotal in understanding diseases such as Crohn's disease and Lyme arthritis. Lyme disease, caused by , is the most prevalent tick-borne illness in the United States, with a substantial number of cases reported annually. While antibiotic treatments are generally effective, approximately 10% of Lyme disease cases develop persistent arthritis, suggesting a dysregulated host immune response. We have previously identified a link between the immunogenic peptidoglycan (PG) and Lyme arthritis and showed that this pathogen sheds significant amounts of PG fragments during growth. Here, we synthesize these PG fragments, including ornithine-containing monosaccharides and disaccharides, to mimic the unique composition of cell walls, using reproducible and rigorous synthetic methods. This synthetic approach allows for the modular preparation of PG derivatives, providing a diverse library of well-defined fragments. These fragments will serve as valuable tools for investigating the role of PG-mediated innate immune response in Lyme disease and aid in the development of improved diagnostic methods and treatment strategies.