{"doi":"10.1016/j.jtha.2023.03.019","title":"Fibrinogen γ′ promotes host survival during Staphylococcus aureus septicemia in mice","abstract":"BackgroundStaphylococcus aureus is a common gram-positive bacterium that is the causative agent for several human diseases, including sepsis. A key virulence mechanism is pathogen binding to host fibrinogen through the C-terminal region of the γ-chain. Previous work demonstrated that FggΔ5 mice expressing mutant fibrinogen γΔ5 lacking a S. aureus binding motif had significantly improved survival following S. aureus septicemia. Fibrinogen γ′ is a human splice variant that represents about 10% to 15% of the total fibrinogen in plasma and circulates as a fibrinogen γ′-γ heterodimer (phFibγ′-γ). The fibrinogen γ′-chain is also expected to lack S. aureus binding function.ObjectiveDetermine if human fibrinogen γ′-γ confers host protection during S. aureus septicemia.MethodsAnalyses of survival and the host response following S. aureus septicemia challenge in FggΔ5 mice and mice reconstituted with purified phFibγ′-γ or phFibγ-γ.ResultsReconstitution of fibrinogen-deficient or wildtype mice with purified phFibγ′-γ prior to infection provided a significant prolongation in host survival relative to mice reconstituted with purified phFibγ-γ, which was superior to that observed with heterozygous FggΔ5 mice. Improved survival could not be accounted for by quantitative differences in fibrinogen-dependent adhesion or clumping, but phFibγ′-γ-containing mixtures generated notably smaller bacterial aggregates. Importantly, administration of phFibγ′-γ after infection also provided a therapeutic benefit by prolonging host survival relative to administration of phFibγ-γ.ConclusionThese findings provide the proof-of-concept that changing the ratio of naturally occurring fibrinogen variants in blood could offer significant therapeutic potential against bacterial infection and potentially other diseases.","journal":"Journal of Thrombosis and Haemostasis","year":2023,"id":357360,"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":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1107210,"name":"Miranda Weggeman","orcid":null,"position":1,"is_corresponding":false},{"id":612644,"name":"Jos Grimbergen","orcid":null,"position":2,"is_corresponding":false},{"id":1095708,"name":"Emily G. Clark","orcid":null,"position":3,"is_corresponding":false},{"id":782135,"name":"Sara Abrahams","orcid":null,"position":4,"is_corresponding":false},{"id":433812,"name":"Woosuk S. Hur","orcid":"0000-0001-5074-6423","position":5,"is_corresponding":false},{"id":1107211,"name":"J. Koopman","orcid":null,"position":6,"is_corresponding":false},{"id":364585,"name":"Matthew J. Flick","orcid":"0000-0002-5034-3162","position":7,"is_corresponding":false},{"id":364578,"name":"Oscar Negrón","orcid":"0000-0002-5234-8397","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:13:34.795336Z","pmid":"37001817","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":[]}