{"doi":"10.1073/pnas.1917576117","title":"<i>Pseudomonas aeruginosa lasR</i>\n                    mutant fitness in microoxia is supported by an Anr-regulated oxygen-binding hemerythrin","abstract":"<i>Pseudomonas aeruginosa</i> strains with loss-of-function mutations in the transcription factor LasR are frequently encountered in the clinic and the environment. Among the characteristics common to LasR-defective (LasR-) strains is increased activity of the transcription factor Anr, relative to their LasR+ counterparts, in low-oxygen conditions. One of the Anr-regulated genes found to be highly induced in LasR- strains was <i>PA14_42860</i> (<i>PA1673</i>), which we named <i>mhr</i> for microoxic hemerythrin. Purified <i>P. aeruginosa</i> Mhr protein contained the predicted di-iron center and bound molecular oxygen with an apparent <i>K</i><sub>d</sub> of ∼1 µM. Both Anr and Mhr were necessary for fitness in <i>lasR</i>+ and <i>lasR</i> mutant strains in colony biofilms grown in microoxic conditions, and the effects were more striking in the <i>lasR</i> mutant. Among genes in the Anr regulon, <i>mhr</i> was most closely coregulated with the Anr-controlled high-affinity cytochrome <i>c</i> oxidase genes. In the absence of high-affinity cytochrome <i>c</i> oxidases, deletion of <i>mhr</i> no longer caused a fitness disadvantage, suggesting that Mhr works in concert with microoxic respiration. We demonstrate that Anr and Mhr contribute to LasR- strain fitness even in biofilms grown in normoxic conditions. Furthermore, metabolomics data indicate that, in a <i>lasR</i> mutant, expression of Anr-regulated <i>mhr</i> leads to differences in metabolism in cells grown on lysogeny broth or artificial sputum medium. We propose that increased Anr activity leads to higher levels of the oxygen-binding protein Mhr, which confers an advantage to <i>lasR</i> mutants in microoxic conditions.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":4196,"datarank":1.4488356664891726,"base_score":4.248495242049359,"endowment":4.248495242049359,"self_citation_contribution":0.637274286307404,"citation_network_contribution":0.8115613801817686,"self_endowment_contribution":0.637274286307404,"citer_contribution":0.8115613801817686,"corpus_percentile":null,"corpus_rank":null,"citation_count":69,"citer_count":47,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0406,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-24","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":40787,"name":"John H. Hammond","orcid":"0000-0002-6121-3291","position":1,"is_corresponding":false},{"id":40788,"name":"Fangfang Zhong","orcid":"0000-0002-8168-6424","position":2,"is_corresponding":false},{"id":40789,"name":"Xiaolei Chen","orcid":"0000-0001-8573-1475","position":3,"is_corresponding":false},{"id":40790,"name":"Caitlin H. Kowalski","orcid":"0000-0002-7222-6987","position":4,"is_corresponding":false},{"id":452,"name":"Alexandra J. Lee","orcid":"0000-0002-0208-3730","position":5,"is_corresponding":false},{"id":40791,"name":"Monique S. Porter","orcid":"0000-0002-5439-0273","position":6,"is_corresponding":false},{"id":42556,"name":"Thomas H. Hampton","orcid":"0000-0003-0543-402X","position":7,"is_corresponding":false},{"id":308,"name":"Casey S. Greene","orcid":"0000-0001-8713-9213","position":8,"is_corresponding":false},{"id":40792,"name":"Ekaterina V. Pletneva","orcid":"0000-0003-1380-2929","position":9,"is_corresponding":false},{"id":456,"name":"Deborah A. Hogan","orcid":"0000-0002-6366-2971","position":10,"is_corresponding":false},{"id":40786,"name":"Michelle E. Clay","orcid":"0000-0002-0377-5405","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}