{"doi":"10.1099/mic.0.001289","title":"Iron homeostasis in Bacillus subtilis relies on three differentially expressed efflux systems","abstract":"In Bacillus subtilis, iron homeostasis is maintained by the ferric uptake regulator (Fur) and manganese homeostasis relies on the manganese transport regulator (MntR). Both Fur and MntR function as bi-functional metalloregulators that repress import and activate metal ion efflux systems. The ferrous iron efflux ATPase, PfeT, is derepressed by hydrogen peroxide (H 2 O 2 ) as sensed by PerR and induced by iron as sensed by Fur. Mutants lacking PfeT are sensitive to iron intoxication. Here, we show that mntR mutants are also iron-sensitive, largely due to decreased expression of the MntR-activated MneP and MneS cation diffusion facilitator (CDF) proteins previously defined for their role in Mn 2+ export. The ability of MneP and MneS to export iron is apparent even when their expression is not induced by Mn 2+ . Our results demonstrate that PfeT, MneP and MneS each contribute to iron homeostasis, and a triple mutant lacking all three is more iron-sensitive than any single mutant. We further show that sensitivity to H 2 O 2 does not correlate with iron sensitivity. For example, an mntR mutant is H 2 O 2 -sensitive due to elevated Mn(II) that increases PerR-mediated repression of peroxide resistance genes, and this repression is antagonized by elevated Fe 2+ in an mntR pfeT mutant. Thus, H 2 O 2 -sensitivity reflects the relative levels of Mn 2+ and Fe 2+ as sensed by the PerR regulatory protein. These results underscore the complex interplay between manganese, iron and oxidative stress in B. subtilis .","journal":"Microbiology","year":2023,"id":342115,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":396634,"name":"Azul Pinochet‐Barros","orcid":null,"position":1,"is_corresponding":false},{"id":338746,"name":"Brian M. Wendel","orcid":"0000-0003-4273-9797","position":2,"is_corresponding":false},{"id":338747,"name":"John D. Helmann","orcid":"0000-0002-3832-3249","position":3,"is_corresponding":false},{"id":1028626,"name":"Caroline H. Steingard","orcid":"0000-0002-8894-8749","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:11:12.506815Z","pmid":"36748638","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":[]}