{"doi":"10.1093/nar/gkaf610","title":"Antitoxin control of optimal transcriptional repression in the atypical HigB–HigA toxin–antitoxin system from <i>Proteus vulgaris</i>","abstract":"Bacterial toxin-antitoxin (TA) pairs transcriptionally autoregulate their expression via a repression/derepression mechanism in response to changing environmental conditions. The structural diversity of TA systems influences the mechanisms of transcriptional regulation. Here, we define the molecular mechanism for the plasmid-encoded HigB-HigA TA pair originally identified in a post-operative infection with antibiotic-resistant Proteus vulgaris. We determine DNA binding and promoter activity by the HigB-HigA complex supported by structural biology and molecular dynamics simulations of an elusive DNA operator-TA repressor complex. To define the optimal oligomeric TA repressor-DNA operator complex required for derepression, we engineered a dedicated trimeric HigB-HigA2 complex that represses transcription more than 26-fold as compared to the tetrameric HigB2-HigA2. These results expand the known diversity of how the HigB-HigA TA family is autoregulated.","journal":"Nucleic Acids Research","year":2025,"id":545408,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":660132,"name":"Marc A. Schureck","orcid":"0000-0001-9880-0783","position":1,"is_corresponding":false},{"id":574869,"name":"Pooja Srinivas","orcid":"0000-0001-7796-8827","position":2,"is_corresponding":false},{"id":1436673,"name":"Taylor M Blackburn","orcid":null,"position":3,"is_corresponding":false},{"id":824871,"name":"Dongxue Wang","orcid":"0000-0002-4402-0690","position":4,"is_corresponding":false},{"id":459762,"name":"Eric D. Hoffer","orcid":"0000-0002-2273-6743","position":5,"is_corresponding":false},{"id":825340,"name":"Michelle Boamah","orcid":null,"position":6,"is_corresponding":false},{"id":1030006,"name":"Kimberly Zaldaña","orcid":"0009-0002-0300-5176","position":7,"is_corresponding":false},{"id":825341,"name":"Nina Onuoha","orcid":null,"position":8,"is_corresponding":false},{"id":825342,"name":"Stacey J. Miles","orcid":null,"position":9,"is_corresponding":false},{"id":917345,"name":"Marcin Grabowicz","orcid":"0000-0001-8000-2222","position":10,"is_corresponding":false},{"id":362425,"name":"C. Denise Okafor","orcid":"0000-0001-7374-1561","position":11,"is_corresponding":false},{"id":17817,"name":"Christine M. Dunham","orcid":"0000-0002-8821-688X","position":12,"is_corresponding":false},{"id":752049,"name":"Ian Pavelich","orcid":"0000-0003-0558-8176","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:53:23.001995Z","pmid":"40671524","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":[]}