{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:16:03Z","timestamp":1787015763227,"version":"build-2736575974"},"reference-count":82,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,9,22]],"date-time":"2024-09-22T00:00:00Z","timestamp":1726963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Mycobacterium abscessus<\/jats:italic>\n (\n Mab<\/jats:italic>\n ) is highly drug resistant, and understanding regulation of antibiotic resistance is critical to future antibiotic development. Regulatory mechanisms controlling\n Mab<\/jats:italic>\n 's \u03b2\u2010lactamase (Bla\n \n Mab<\/jats:italic>\n <\/jats:sub>\n ) that mediates \u03b2\u2010lactam resistance remain unknown.\n S. aureus<\/jats:italic>\n encodes a prototypical protease\u2010mediated two\u2010component system BlaRI regulating the \u03b2\u2010lactamase BlaZ. BlaR binds extracellular \u03b2\u2010lactams, activating an intracellular peptidase domain which cleaves BlaI to derepress\n blaZ<\/jats:italic>\n .\n Mycobacterium tuberculosis<\/jats:italic>\n (\n Mtb<\/jats:italic>\n ) encodes homologs of BlaRI (which we will denote as BlaIR to reflect the inverted gene order in mycobacteria) that regulate not only the\n Mtb<\/jats:italic>\n \u03b2\u2010lactamase,\n blaC<\/jats:italic>\n , but also additional genes related to respiration. We identified orthologs of\n blaIR<\/jats:italic>\n \n Mtb<\/jats:italic>\n <\/jats:sub>\n in\n Mab<\/jats:italic>\n and hypothesized that they regulate\n bla<\/jats:italic>\n \n Mab<\/jats:italic>\n <\/jats:sub>\n . Surprisingly, neither deletion of\n blaIR<\/jats:italic>\n \n Mab<\/jats:italic>\n <\/jats:sub>\n nor overexpression of only\n blaI<\/jats:italic>\n \n Mab<\/jats:italic>\n <\/jats:sub>\n altered\n bla<\/jats:italic>\n \n Mab<\/jats:italic>\n <\/jats:sub>\n expression or \u03b2\u2010lactam susceptibility. However, BlaI\n \n Mab<\/jats:italic>\n <\/jats:sub>\n did bind to conserved motifs upstream of several\n Mab<\/jats:italic>\n genes involved in respiration, yielding a putative regulon that partially overlapped with BlaI\n \n Mtb<\/jats:italic>\n <\/jats:sub>\n . Prompted by evidence that respiration inhibitors including clofazimine induce the BlaI regulon in\n Mtb<\/jats:italic>\n , we found that clofazimine triggers induction of\n blaIR<\/jats:italic>\n \n Mab<\/jats:italic>\n <\/jats:sub>\n and its downstream regulon. Highlighting an important role for BlaIR\n \n Mab<\/jats:italic>\n <\/jats:sub>\n in adapting to disruptions in energy metabolism, constitutive repression of the BlaI\n \n Mab<\/jats:italic>\n <\/jats:sub>\n regulon rendered\n Mab<\/jats:italic>\n highly susceptible to clofazimine. In addition to our unexpected findings that BlaIR\n \n Mab<\/jats:italic>\n <\/jats:sub>\n does not regulate \u03b2\u2212lactam resistance, this study highlights the novel role of mycobacterial BlaRI\u2010type regulators in regulating electron transport and respiration.\n <\/jats:p>","DOI":"10.1111\/mmi.15314","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T02:45:42Z","timestamp":1727059542000},"page":"583-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Atypical\n Mycobacterium abscessus<\/i>\n BlaRI<\/scp>\n Ortholog Mediates Regulation of Energy Metabolism but Not \u03b2\u2010Lactam Resistance"],"prefix":"10.1111","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3283-9751","authenticated-orcid":false,"given":"Lauren\u00a0E.","family":"Bonefont","sequence":"first","affiliation":[{"name":"Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine University of Central Florida Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5801-6549","authenticated-orcid":false,"given":"Haley\u00a0C.","family":"Davenport","sequence":"additional","affiliation":[{"name":"Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine University of Central Florida Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-3559","authenticated-orcid":false,"given":"Catherine\u00a0T.","family":"Chaton","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2182-6843","authenticated-orcid":false,"given":"Konstantin\u00a0V.","family":"Korotkov","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-3238","authenticated-orcid":false,"given":"Kyle\u00a0H.","family":"Rohde","sequence":"additional","affiliation":[{"name":"Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine University of Central Florida Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00849-w"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05583-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02621-12"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8754"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.17582\/journal.vsrr\/2018\/4.2.43.54"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406796200"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.5b00086"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw426"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.011076"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316894110"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1125"},{"issue":"110","key":"e_1_2_10_14_1","article-title":"Proteogenomic Analysis of Polymorphisms and Gene Annotation Divergences in Prokaryotes Using a Clustered Mass Spectrometry\u2010Friendly Database","volume":"10","author":"Souza G. 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