{"doi":"10.1101/2021.09.13.460140","title":"Alpha-Gal Syndrome: Involvement of <i>Amblyomma americanum</i> α-D-galactosidase and α-1,4 Galactosyltransferase enzymes in α-gal metabolism","abstract":"Abstract Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-⍰-1,3-galactose (α-gal) injected into humans from the lone star tick ( Amblyomma americanum ) bite. This study aims at the functional characterization of two tick enzymes, α-D-galactosidase (ADGal) and α-1,4 galactosyltransferase (β-1,4GalT) in α-gal metabolism. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars: GlcNAc, Glc, and Xyl in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in Am. americanum to examine their functional role in α-gal metabolism and AGS onset. Silencing of ADGal led to the significant down regulation of genes involved in galactose metabolism and transport in Am. americanum . Immunoblot and N-glycan analysis of the Am. americanum salivary glands showed a significant reduction in ⍰-gal levels in silenced tissues. However, there was no significant difference in the level of ⍰-gal in β-1,4GalT silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal silenced salivary glands. These results provide an insight into the role of α-D galactosidase &amp; β-1,4GalT in tick biology and the probable involvement in the onset of AGS.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226642,"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":0.9627,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":692113,"name":"Gary Crispell","orcid":"0000-0003-0417-6305","position":1,"is_corresponding":false},{"id":692114,"name":"Ahmed A. Mohamed","orcid":"0000-0001-7369-3117","position":2,"is_corresponding":false},{"id":692997,"name":"Cameron Cox","orcid":null,"position":3,"is_corresponding":false},{"id":692998,"name":"Joshua Lange","orcid":null,"position":4,"is_corresponding":false},{"id":463637,"name":"Shailesh K. Choudhary","orcid":"0000-0002-8160-6711","position":5,"is_corresponding":false},{"id":463642,"name":"Scott P. Commins","orcid":"0000-0003-1198-2428","position":6,"is_corresponding":false},{"id":288555,"name":"Shahid Karim","orcid":"0000-0001-5596-3304","position":7,"is_corresponding":false},{"id":645805,"name":"Surendra Raj Sharma","orcid":"0000-0002-9602-2874","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:54:38.004707Z","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":[]}