{"doi":"10.1101/2022.08.23.504964","title":"Oxidative reactions catalyzed by hydrogen peroxide produced by <i>Streptococcus pneumoniae</i> and other Streptococci Cause the Release and Degradation of Heme from Hemoglobin","abstract":"Abstract Streptococcus pneumoniae (Spn) strains cause pneumonia that kills millions every year worldwide. Spn produces Ply, a hemolysin that lyses erythrocytes releasing hemoglobin and also produces the pro-oxidant hydrogen peroxide (Spn-H 2 O 2 ) during growth. The hallmark of the pathophysiology of hemolytic diseases is the oxidation of hemoglobin but oxidative reactions catalyzed by Spn-H 2 O 2 has been poorly studied. We characterized the oxidation of hemoglobin by Spn-H 2 O 2 . We prepared a series of single (Δ spxB , or Δ lctO ), double mutant (Δ spxB Δ lctO ) and complemented strains in TIGR4, D39 and EF3030. We then utilized an in vitro model with oxy-hemoglobin to demonstrate that oxy-hemoglobin was oxidized rapidly, within 30 min of incubation, by Spn-H 2 O 2 to met-hemoglobin and that the main source of Spn-H 2 O 2 was pyruvate oxidase (SpxB). Moreover, extended incubation caused the release and the degradation of heme. We then assessed oxidation of hemoglobin and heme degradation by other bacteria inhabitants of the respiratory tract. All hydrogen peroxide-producing streptococci tested caused the oxidation of hemoglobin and heme degradation whereas those bacterial species that produce &lt;1 μM H 2 O 2 , neither oxidized hemoglobin nor degraded heme. An ex vivo bacteremia model confirmed that oxidation of hemoglobin and heme degradation occurred concurrently with hemoglobin that was released from erythrocytes by Ply. Finally, gene expression studies demonstrated that heme, but not red blood cells or hemoglobin induced an upregulated transcription of the spxB gene. Oxidation of hemoglobin may be important for pathogenesis and for the symbiosis of hydrogen peroxide-producing bacteria with other species by providing nutrients such as iron.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301752,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"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":570945,"name":"Anna Scasny","orcid":"0000-0003-3567-1157","position":1,"is_corresponding":false},{"id":570944,"name":"Faidad Khan","orcid":"0000-0002-3394-2411","position":2,"is_corresponding":false},{"id":993774,"name":"Aidan Creel","orcid":null,"position":3,"is_corresponding":false},{"id":993775,"name":"Perriann Smith","orcid":null,"position":4,"is_corresponding":false},{"id":814809,"name":"Ana G. Jop Vidal","orcid":null,"position":5,"is_corresponding":false},{"id":993202,"name":"Fa’alataitaua M. Fitisemanu","orcid":"0000-0002-9449-1327","position":6,"is_corresponding":false},{"id":397527,"name":"Teresita Padilla‐Benavides","orcid":"0000-0002-4624-0822","position":7,"is_corresponding":false},{"id":263683,"name":"Jeffrey N. Weiser","orcid":"0000-0001-7168-8090","position":8,"is_corresponding":false},{"id":449056,"name":"Jorge E. Vidal","orcid":"0000-0003-0573-5658","position":9,"is_corresponding":false},{"id":814810,"name":"Babek Alibayov","orcid":null,"position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","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":[]}