{"doi":"10.54014/rtsk-x316","title":"Molecular mechanisms shaping host range of a vector-borne pathogen","abstract":"Vector-borne diseases, such as Lyme disease caused by Borrelia burgdorferi sensu lato (Bbsl), have narrow host ranges and are apt models to study host-microparasite coevolution. Some species and strains of Lyme borreliae (LB) are specialists, infecting only mammalian or only avian hosts (ex. Borrelia afzelii and B. garinii, respectively), while others are generalists and infect both hosts (ex. B. burgdorferi). Such host tropisms are hypothesized to be partially shaped by the ability of these pathogens evade host immune defenses, such as complement. Complement is a first line host defense against invading pathogens that kills LB in vitro and inhibits spirochete infection in vivo. In fact, complement can be activated within hours upon spirochete invasion, and different species and strains of LB vary in their ability to evade complement of different host species. We thus hypothesized tick-to-host transmission of LB is dependent on the spirochetes’ ability to evade complement-mediated killing in tick blood meals, and that variation in this ability leads to host-specific transmission. It is difficult to study host-specific survival in the blood meals taken from relevant hosts due to issues with maintaining and using wild-caught or atypical animal models representing natural reservoir hosts, such as the lack of proper facilities or appropriate reagents. We overcome these issues with an artificial membrane feeding model, which allows us to feed ticks on blood of different vertebrate hosts and manipulate the complement in the blood. We used this model and live host models to investigate the impact of complement on tick-to-host transmission by feeding I. scapularis nymphs infected with B. burgdorferi ss, B. garinii, or B. afzelii on avian or mammalian blood and hosts, with or without complement. We observed differences in these strains’ ability to survive complement in feeding ticks and transmit to hosts or blood. These differences correlated with aforementioned host tropisms, indicating the source of complement in the blood meal dictates tick-to-host transmission success defining LB host tropisms. We next sought to determine the molecular mechanisms by which complement defines host tropisms. We focused on a polymorphic spirochete-produced protein, CspA, as this protein is produced when spirochetes are in ticks, and binds to the host complement inhibitor, Factor H (FH), to facilitate spirochete complement evasion in vitro. When we fed ticks carrying isogenic strains of B. burgdorferi ss producing different CspA variants on mammalian and avian blood and hosts, we found isogenic strains producing CspA variants of B. burgdorferi","journal":"Scholars Archive - University at Albany (University at Albany, State University of New York)","year":2020,"id":144879,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":539151,"name":"Thomas C. Hart","orcid":"0000-0003-4369-3962","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:48.191325Z","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":[]}