{"doi":"10.1093/nar/gkaf063","title":"A phosphorylation signal activates genome-wide transcriptional control by BfmR, the global regulator of <i>Acinetobacter</i> resistance and virulence","abstract":"The nosocomial pathogen Acinetobacter baumannii is a major threat to human health. The sensor kinase-response regulator system, BfmS-BfmR, is essential to multidrug resistance and virulence in the bacterium and represents a potential antimicrobial target. Important questions remain about how the system controls resistance and pathogenesis. Although BfmR knockout alters expression of >1000 genes, its direct regulon is undefined. Moreover, how phosphorylation controls the regulator is unclear. Here, we address these problems by combining mutagenesis, ChIP-seq, and in vitro phosphorylation to study the functions of phospho-BfmR. We show that phosphorylation is required for BfmR-mediated gene regulation, antibiotic resistance, and sepsis development in vivo. Consistent with activating the protein, phosphorylation induces dimerization and target DNA affinity. Integrated analysis of genome-wide binding and transcriptional profiles of BfmR led to additional key findings: (1) Phosphorylation dramatically expands the number of genomic sites BfmR binds; (2) DNA recognition involves a direct repeat motif widespread across promoters; (3) BfmR directly regulates 303 genes as activator (e.g., capsule, peptidoglycan, and outer membrane biogenesis) or repressor (pilus biogenesis); (4) BfmR controls several non-coding sRNAs. These studies reveal the centrality of a phosphorylation signal in driving A. baumannii disease and disentangle the extensive pathogenic gene-regulatory network under its control.","journal":"Nucleic Acids Research","year":2025,"id":513193,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"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":649965,"name":"Yunfei Dai","orcid":"0000-0003-1995-9126","position":1,"is_corresponding":false},{"id":656164,"name":"Akira Iinishi","orcid":null,"position":2,"is_corresponding":false},{"id":1215803,"name":"Arpita Mohapatra","orcid":"0000-0003-4495-3789","position":3,"is_corresponding":false},{"id":1336866,"name":"Mark W. Soo","orcid":null,"position":4,"is_corresponding":false},{"id":1336867,"name":"Everett Hay","orcid":null,"position":5,"is_corresponding":false},{"id":1030768,"name":"Gabrielle M. Hernandez","orcid":"0009-0005-0494-0467","position":6,"is_corresponding":false},{"id":649968,"name":"Edward Geisinger","orcid":"0000-0001-9661-8072","position":7,"is_corresponding":false},{"id":978731,"name":"Nicole Raustad","orcid":null,"position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:48:17.908238Z","pmid":"39921563","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":[]}