{"doi":"10.1101/2025.04.12.648518","title":"The response regulator BqsR/CarR controls ferrous iron (Fe <sup>2+</sup> ) acquisition in <i>Pseudomonas aeruginosa</i>","abstract":"Abstract Pseudomonas aeruginosa is a ubiquitous, Gram-negative bacterium that forms biofilms and is responsible for antibiotic-resistant hospital-acquired infections in humans. The P. aeruginosa BqsRS two-component system regulates biofilm formation and dispersal by sensing extracytoplasmic Fe 2+ , but the mechanistic details of this process are poorly understood. In this work, we report the crystal and solution structures of the Pa BqsR response regulator receiver domain, comprising a (βα) 5 response regulator assembly, and the DNA-binding domain, comprising a helix-turn-helix motif. Consistent with its cognate stimulus being Fe 2+ , we show that Pa BqsR binds directly to the promoter region of the feo operon that encodes the bacterial Fe 2+ transport system FeoABC. Corroborating these in vitro results, transcriptional studies show that Pa BqsR is a global regulator controlling many important genes in PAO1, including the feo operon. Intriguingly, promoter-based assays reveal that Pa BqsR is a dynamic regulator that responds to bioavailable Fe 2+ , likely through the ability of Pa BqsR to bind Fe 2+ directly via a His-rich motif, independent of the Pa BqsS membrane His kinase. This mode of regulation is unprecedented among OmpR-like response regulators but represents an important level of control over Fe 2+ acquisition in P. aeruginosa that could be an attractive therapeutic target to treat hospital-acquired infections.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":564197,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"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":1467305,"name":"Harvinder Singh","orcid":"0000-0002-8686-2802","position":1,"is_corresponding":false},{"id":786801,"name":"Harvinder Singh","orcid":"0000-0002-6349-3143","position":2,"is_corresponding":false},{"id":1467635,"name":"Darryn Greene","orcid":null,"position":3,"is_corresponding":false},{"id":1467636,"name":"Ahmed O. Tajudeen","orcid":null,"position":4,"is_corresponding":false},{"id":920102,"name":"Aya Kubo","orcid":null,"position":5,"is_corresponding":false},{"id":1467637,"name":"Sara Patamawenu","orcid":null,"position":6,"is_corresponding":false},{"id":1152905,"name":"Rachel Kramer","orcid":"0000-0001-5698-0712","position":7,"is_corresponding":false},{"id":1467638,"name":"Janae Baptiste Brown","orcid":null,"position":8,"is_corresponding":false},{"id":534878,"name":"Kelly N. Chacón","orcid":"0000-0003-1332-7283","position":9,"is_corresponding":false},{"id":919578,"name":"Marianna A. Patrauchan","orcid":"0000-0002-0495-3867","position":10,"is_corresponding":false},{"id":640506,"name":"Aaron T. Smith","orcid":"0000-0002-9332-8683","position":11,"is_corresponding":false},{"id":1119502,"name":"Alexander Paredes","orcid":null,"position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:56:20.933088Z","pmid":"41279889","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":[]}