{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:41:11Z","timestamp":1792593671630,"version":"4.5.0"},"reference-count":220,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Regulated gene expression in bacteria accommodates demands imposed by different environments. In addition to ensuring the production of required metabolic and structural components, gene regulation protects bacteria against the adverse effects of misexpression. Upon encountering a novel environment, such as sustained exposure to antibiotics, transcriptional recalibration ensues to improve fitness. For antibiotics, this involves enhancing the expression of an existing repertoire of resistance mechanisms and is often mediated by mutations in regulators of gene expression. Here, we review how diverse gene regulatory mutations confer antibiotic resistance to bacterial pathogens. We view these strategies through the lens of the Gene Expression Demand Theory, originally proposed for inducible operons involved in sugar metabolism, and describe the molecular basis and evolutionary consequences for a few well-studied examples. Broad underlying preferences of when and which kind of regulatory mutations bacteria employ emerge from these examples. A key pattern appears to be a preference for derepression rather than activating mutations, and we highlight potential underlying genetic and evolutionary explanations. Finally, even as our knowledge of molecular mechanisms of antibiotic adaptation continues to expand, we propose that adaptation by regulatory mutations provides a framework for assessing the risk of resistance evolution in the case of novel antibiotics and alternative targets for diagnostic and therapeutic interventions.<\/jats:p>","DOI":"10.1093\/genetics\/iyag278","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:59:16Z","timestamp":1792591156000},"source":"Crossref","is-referenced-by-count":0,"title":["Meeting gene expression demand during evolution of antibiotic resistance"],"prefix":"10.1093","author":[{"given":"Rhea","family":"Vinchhi","sequence":"first","affiliation":[{"name":"Department of Biology, Indian Institute of Science Education and Research (IISER) , Pune 411008, Maharashtra ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2947-3931","authenticated-orcid":false,"given":"Nishad","family":"Matange","sequence":"additional","affiliation":[{"name":"Department of Biology, Indian Institute of Science Education and Research (IISER) , Pune 411008, Maharashtra ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"2026102109591415400_iyag278-B1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12091447","article-title":"Pseudouridine synthase RsuA confers a survival advantage to bacteria under streptomycin stress","volume":"12","author":"Abedeera","year":"2023","journal-title":"Antibiotics (Basel)"},{"key":"2026102109591415400_iyag278-B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011287","article-title":"Queuosine biosynthetic enzyme, QueE moonlights as a cell division regulator","volume":"20","author":"Adeleye","year":"2024","journal-title":"PLoS Genet"},{"key":"2026102109591415400_iyag278-B3","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1128\/AAC.41.10.2067","article-title":"Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon","volume":"41","author":"Alekshun","year":"1997","journal-title":"Antimicrob Agents Chemother"},{"key":"2026102109591415400_iyag278-B4","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00095-25","article-title":"A mechanistic understanding of the effect of Staphylococcus aureus VraS histidine kinase single-point mutation on antibiotic resistance","volume":"13","author":"Ali","year":"2025","journal-title":"Microbiol Spectr"},{"key":"2026102109591415400_iyag278-B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004500","article-title":"Silencing by H-NS potentiated the evolution of Salmonella","volume":"10","author":"Ali","year":"2014","journal-title":"PLoS Pathog"},{"key":"2026102109591415400_iyag278-B6","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1111\/j.1365-2958.2011.07547.x","article-title":"Downregulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis","volume":"79","author":"Ando","year":"2011","journal-title":"Mol Microbiol"},{"key":"2026102109591415400_iyag278-B7","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8111716","article-title":"Colistin update on its mechanism of action and resistance, present and future challenges","volume":"8","author":"Andrade","year":"2020","journal-title":"Microorganisms"},{"key":"2026102109591415400_iyag278-B8","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202516608","article-title":"The histidine kinase VraS interacts with vancomycin and penicillins through its membrane-anchored N-terminal domain","volume":"65","author":"Antinori","year":"2026","journal-title":"Angew Chem Int Ed Engl"},{"key":"2026102109591415400_iyag278-B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3003443","article-title":"Impeding pathways of intrinsic resistance in Escherichia coli confers antibiotic sensitization and resistance proofing","volume":"23","author":"Balachandran","year":"2025","journal-title":"PLoS Biol"},{"key":"2026102109591415400_iyag278-B10","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlad018","article-title":"Molecular diagnostics for genotypic detection of antibiotic resistance: current landscape and future directions","volume":"5","author":"Banerjee","year":"2023","journal-title":"JAC Antimicrob Resist"},{"key":"2026102109591415400_iyag278-B11","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1128\/AAC.42.9.2352","article-title":"Salmonella enteritidis: ampC plasmid-mediated inducible \u03b2-lactamase (DHA-1) with an ampR gene from Morganella morganii","volume":"42","author":"Barnaud","year":"1998","journal-title":"Antimicrob. 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