{"doi":"10.1016/j.celrep.2021.109267","title":"Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza","abstract":"Streptococcus pneumoniae (Spn) alone and during co-infection with influenza A virus (IAV) can result in severe pneumonia with mortality. Pneumococcal surface protein A (PspA) is an established virulence factor required for Spn evasion of lactoferricin and C-reactive protein-activated complement-mediated killing. Herein, we show that PspA functions as an adhesin to dying host cells. We demonstrate that PspA binds to host-derived glyceraldehyde-3-phosphate dehydrogenase (GAPDH) bound to outward-flipped phosphatidylserine residues on dying host cells. PspA-mediated adhesion was to apoptotic, pyroptotic, and necroptotic cells, but not healthy lung cells. Using isogenic mutants of Spn, we show that PspA-GAPDH-mediated binding to lung cells increases pneumococcal localization in the lower airway, and this is enhanced as a result of pneumolysin exposure or co-infection with IAV. PspA-mediated binding to GAPDH requires amino acids 230-281 in its α-helical domain with intratracheal inoculation of this PspA fragment alongside the bacteria reducing disease severity in an IAV/Spn pneumonia model.","journal":"Cell Reports","year":2021,"id":157214,"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":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"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":371689,"name":"Norberto González-Juarbe","orcid":"0000-0003-2481-698X","position":1,"is_corresponding":false},{"id":313639,"name":"Ashleigh N. Riegler","orcid":"0000-0001-7939-6121","position":2,"is_corresponding":false},{"id":663563,"name":"Hansol Im","orcid":"0000-0002-0629-7461","position":3,"is_corresponding":false},{"id":664228,"name":"Yvette Hale","orcid":null,"position":4,"is_corresponding":false},{"id":570169,"name":"Maryann P. Platt","orcid":"0000-0001-8900-1226","position":5,"is_corresponding":false},{"id":663564,"name":"Christina M. Croney","orcid":"0000-0001-6574-8325","position":6,"is_corresponding":false},{"id":419410,"name":"David E. Briles","orcid":null,"position":7,"is_corresponding":false},{"id":259879,"name":"Carlos J. Orihuela","orcid":"0000-0002-8542-4069","position":8,"is_corresponding":false},{"id":663562,"name":"Sang‐Sang Park","orcid":"0000-0002-5961-9508","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:44:17.471040Z","pmid":"34133917","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":[]}