{"doi":"10.1371/journal.ppat.1013849","title":"Peptidoglycan architecture dictates protein interactions, tissue tropism, and arthritis in the Lyme disease spirochete Borrelia burgdorferi","abstract":"<jats:p>\n                    Lyme disease is a vector-borne illness transmitted by infected\n                    <jats:italic>Ixodes spp.</jats:italic>\n                    ticks. Dissemination of the Lyme spirochete—\n                    <jats:italic>Borrelia burgdorferi—</jats:italic>\n                    from the tick bite site results in a bi-phasic infection; the latter phase can cause severe musculoskeletal disease including arthritis. Lyme arthritis is an inflammatory disorder and maladaptive immune response to\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    infection and its cellular products. One such product, which has been implicated as a key mediator of Lyme arthritis, is peptidoglycan. Peptidoglycan (PG) is a near ubiquitous feature of the bacterial cell envelope, but several chemical features make\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    PG distinct from other members of the kingdom. We hypothesized the overall chemical composition and structural architecture of the\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    cell wall are essential to Lyme disease pathogenesis. To manipulate the PG peptide chemical composition, as well as the native cross-links, we produced an isogenic deletion of a putative PG carboxypeptidase\n                    <jats:italic>dacA</jats:italic>\n                    homologue and assessed both the molecular and cellular phenotypes while probing the pathogenicity of our mutant strain. Our combined and comprehensive approach indicates while changes to PG stem peptide and cross-linking have virtually no discernable impact on any\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    characteristic in vitro, alterations have significant impacts on tissue tropism and result in a near complete attenuation of Lyme arthritis. PG sacculi containing increased amounts of free and cross-linked pentapeptide surprisingly caused the disassociation of p83/100, an abundant periplasmic protein of unknown function previously implicated in joint tropism, likely contributing to a marked decrease in pathogenicity. These studies strengthen our understanding of the\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    cell envelope, its unusual components, and further define bacterial features that mediate infectious arthritis.\n                  </jats:p>","journal":"PLOS Pathogens","year":2026,"id":670543,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1181461,"name":"Osamudiamen Ebohon","orcid":"0000-0003-3547-6933","position":1,"is_corresponding":false},{"id":627755,"name":"Mecaila E. McClune","orcid":"0000-0002-9071-540X","position":2,"is_corresponding":false},{"id":859533,"name":"Rebecca N. Trimble","orcid":"0000-0001-5980-0043","position":3,"is_corresponding":false},{"id":1097000,"name":"Casey N. Kellogg","orcid":"0009-0009-1503-838X","position":4,"is_corresponding":false},{"id":374037,"name":"Carmen J. Booth","orcid":"0000-0002-2153-738X","position":5,"is_corresponding":false},{"id":822178,"name":"Wolfram R. Zückert","orcid":"0000-0002-7350-2162","position":6,"is_corresponding":false},{"id":627751,"name":"Brandon L. Jutras","orcid":"0000-0002-7989-1031","position":7,"is_corresponding":false},{"id":1309314,"name":"Saadman S. Ahmad","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Peptidoglycan architecture dictates protein interactions, tissue tropism, and arthritis in the Lyme disease spirochete Borrelia burgdorferi","abstract":"<jats:p>\n                    Lyme disease is a vector-borne illness transmitted by infected\n                    <jats:italic>Ixodes spp.</jats:italic>\n                    ticks. Dissemination of the Lyme spirochete—\n                    <jats:italic>Borrelia burgdorferi—</jats:italic>\n                    from the tick bite site results in a bi-phasic infection; the latter phase can cause severe musculoskeletal disease including arthritis. Lyme arthritis is an inflammatory disorder and maladaptive immune response to\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    infection and its cellular products. One such product, which has been implicated as a key mediator of Lyme arthritis, is peptidoglycan. Peptidoglycan (PG) is a near ubiquitous feature of the bacterial cell envelope, but several chemical features make\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    PG distinct from other members of the kingdom. We hypothesized the overall chemical composition and structural architecture of the\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    cell wall are essential to Lyme disease pathogenesis. To manipulate the PG peptide chemical composition, as well as the native cross-links, we produced an isogenic deletion of a putative PG carboxypeptidase\n                    <jats:italic>dacA</jats:italic>\n                    homologue and assessed both the molecular and cellular phenotypes while probing the pathogenicity of our mutant strain. Our combined and comprehensive approach indicates while changes to PG stem peptide and cross-linking have virtually no discernable impact on any\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    characteristic in vitro, alterations have significant impacts on tissue tropism and result in a near complete attenuation of Lyme arthritis. PG sacculi containing increased amounts of free and cross-linked pentapeptide surprisingly caused the disassociation of p83/100, an abundant periplasmic protein of unknown function previously implicated in joint tropism, likely contributing to a marked decrease in pathogenicity. These studies strengthen our understanding of the\n                    <jats:italic>B. burgdorferi</jats:italic>\n                    cell envelope, its unusual components, and further define bacterial features that mediate infectious arthritis.\n                  </jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41557633","pmcid":"PMC12818604","openalex_id":"https://openalex.org/W7124844698","authors":[],"funders":[{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"R01AI173256, R01AI178711, P01AI181934","title":null},{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"R21AI173835","title":null},{"funder_name":"U.S. Department of Agriculture","grant_id":"VA-160113","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI173256","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI178711","title":null},{"funder_name":"Bay Area Lyme Foundation","grant_id":"","title":null},{"funder_name":"Global Lyme Alliance","grant_id":"","title":null},{"funder_name":"Steven and Alexandra Cohen Foundation","grant_id":"","title":null}],"total_grants":8,"fwci":21.5353,"citation_percentile":0.98779399,"influential_citations":0,"citation_trend":[{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1013849&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1013849&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.ppat.1013849","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.ppat.1013849","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41557633","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41557633/","host_type":"repository"},{"url":"https://doaj.org/article/96b92c7d57f241a486b809fd04b299a3","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12818604/pdf/ppat.1013849.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12818604","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12818604?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Vector-borne infectious diseases","Heat shock proteins research","Trypanosoma species research and implications"],"mesh_terms":["Host Tropism","Animals","Arthritis, Infectious","Bacterial Proteins","Cell Wall","Humans","Lyme Disease","Peptidoglycan","Borrelia burgdorferi","Mice"],"keywords":["Borrelia burgdorferi","Lyme disease","Peptidoglycan","Immune system","Tissue tropism","Periplasmic space","Arthritis","LYME"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-15T22:38:49.468286Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}