{"doi":"10.26508/lsa.202201441","title":"The intracellular pathogen <i>Francisella tularensis</i> escapes from adaptive immunity by metabolic adaptation","abstract":"Intracellular pathogens lose many metabolic genes during their evolution from free-living bacteria, but the pathogenic consequences of their altered metabolic programs on host immunity are poorly understood. Here, we show that a pathogenic strain of Francisella tularensis subsp. tularensis (FT) has five amino acid substitutions in RibD, a converting enzyme of the riboflavin synthetic pathway responsible for generating metabolites recognized by mucosal-associated invariant T (MAIT) cells. Metabolites from a free-living strain, F. tularensis subsp. novicida (FN), activated MAIT cells in a T-cell receptor (TCR)–dependent manner, whereas introduction of FT-type ribD to the free-living strain was sufficient to attenuate this activation in both human and mouse MAIT cells. Intranasal infection in mice showed that the ribD FT -expressing FN strain induced impaired Th1-type MAIT cell expansion and resulted in reduced bacterial clearance and worsened survival compared with the wild-type free-living strain FN. These results demonstrate that F. tularensis can acquire immune evasion capacity by alteration of metabolic programs during evolution.","journal":"Life Science Alliance","year":2022,"id":270911,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":934687,"name":"Takashi Shimizu","orcid":"0000-0003-1294-0799","position":1,"is_corresponding":false},{"id":936332,"name":"Mashio Nakahara","orcid":null,"position":2,"is_corresponding":false},{"id":935680,"name":"Emi Ito","orcid":"0000-0001-9401-243X","position":3,"is_corresponding":false},{"id":935681,"name":"François Legoux","orcid":"0000-0003-4304-7637","position":4,"is_corresponding":false},{"id":936333,"name":"Shotaro Fujii","orcid":null,"position":5,"is_corresponding":false},{"id":936334,"name":"Yuka Yamada","orcid":null,"position":6,"is_corresponding":false},{"id":934692,"name":"Makoto Furutani‐Seiki","orcid":"0000-0002-0885-4778","position":7,"is_corresponding":false},{"id":232585,"name":"Olivier Lantz","orcid":"0000-0003-3161-7719","position":8,"is_corresponding":false},{"id":459021,"name":"Sho Yamasaki","orcid":"0000-0002-5184-6917","position":9,"is_corresponding":false},{"id":935682,"name":"Masahisa Watarai","orcid":"0000-0003-3477-3135","position":10,"is_corresponding":false},{"id":935232,"name":"Mutsunori Shirai","orcid":null,"position":11,"is_corresponding":false},{"id":754574,"name":"Kensuke Shibata","orcid":"0000-0001-8794-7368","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T00:27:35.206187Z","pmid":"35667686","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":[]}