{"doi":"10.1093/nar/gkac743","title":"Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses of <i>Pseudomonas aeruginosa</i>","abstract":"Pseudomonas aeruginosa is an opportunistic pathogen and major cause of hospital-acquired infections. The virulence of P. aeruginosa is largely determined by its transcriptional regulatory network (TRN). We used 411 transcription profiles of P. aeruginosa from diverse growth conditions to construct a quantitative TRN by identifying independently modulated sets of genes (called iModulons) and their condition-specific activity levels. The current study focused on the use of iModulons to analyze the biofilm production and antibiotic resistance of P. aeruginosa. Our analysis revealed: (i) 116 iModulons, 81 of which show strong association with known regulators; (ii) novel roles of regulators in modulating antibiotics efflux pumps; (iii) substrate-efflux pump associations; (iv) differential iModulon activity in response to beta-lactam antibiotics in bacteriological and physiological media; (v) differential activation of 'Cell Division' iModulon resulting from exposure to different beta-lactam antibiotics and (vi) a role of the PprB iModulon in the stress-induced transition from planktonic to biofilm lifestyle. In light of these results, the construction of an iModulon-based TRN provides a transcriptional regulatory basis for key aspects of P. aeruginosa infection, such as antibiotic stress responses and biofilm formation. Taken together, our results offer a novel mechanistic understanding of P. aeruginosa virulence.","journal":"Nucleic Acids Research","year":2022,"id":246870,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"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":442184,"name":"Hannah Tsunemoto","orcid":"0000-0002-1546-097X","position":1,"is_corresponding":false},{"id":559194,"name":"Anand V. Sastry","orcid":"0000-0002-8293-3909","position":2,"is_corresponding":false},{"id":442185,"name":"Richard Szubin","orcid":"0000-0002-1212-8728","position":3,"is_corresponding":false},{"id":812990,"name":"Kevin Rychel","orcid":"0000-0002-4769-2804","position":4,"is_corresponding":false},{"id":225824,"name":"Siddharth Chauhan","orcid":"0000-0001-6674-895X","position":5,"is_corresponding":false},{"id":244710,"name":"Joe Pogliano","orcid":"0000-0001-8989-2655","position":6,"is_corresponding":false},{"id":5441,"name":"Bernhard Ø. Palsson","orcid":"0000-0003-2357-6785","position":7,"is_corresponding":false},{"id":567001,"name":"Akanksha Rajput","orcid":"0000-0001-8176-6697","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T00:23:48.622830Z","pmid":"36095122","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":[]}