{"doi":"10.1128/iai.00440-23","title":"Progress toward a vaccine for extraintestinal pathogenic <i>E. coli</i> (ExPEC) II: efficacy of a toxin-autotransporter dual antigen approach","abstract":"ABSTRACT Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen’s pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of &gt;20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease.","journal":"Infection and Immunity","year":2024,"id":455648,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":465023,"name":"Justin R. Clark","orcid":"0000-0003-1590-6828","position":1,"is_corresponding":false},{"id":676715,"name":"James D. Chang","orcid":"0000-0003-3211-3299","position":2,"is_corresponding":false},{"id":683378,"name":"Jacob J. Zulk","orcid":"0000-0002-3758-5503","position":3,"is_corresponding":false},{"id":1106041,"name":"Dylan M. Chirman","orcid":"0000-0002-7178-6333","position":4,"is_corresponding":false},{"id":687818,"name":"Felipe-Andrés Piedra","orcid":"0000-0002-0100-2919","position":5,"is_corresponding":false},{"id":676716,"name":"Ellen E. Vaughan","orcid":"0000-0002-3391-7873","position":6,"is_corresponding":false},{"id":1280167,"name":"Haroldo J. Hernandez Santos","orcid":null,"position":7,"is_corresponding":false},{"id":225239,"name":"Kathryn A. Patras","orcid":"0000-0003-2631-8810","position":8,"is_corresponding":false},{"id":363659,"name":"Anthony W. Maresso","orcid":"0000-0002-4452-3490","position":9,"is_corresponding":false},{"id":465025,"name":"Yikun Xing","orcid":"0000-0002-9778-5507","position":0,"is_corresponding":true}],"reference_count":141,"raw_metadata":null,"created_at":"2026-07-19T02:03:22.974789Z","pmid":"38591882","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":[]}