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However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds.<\/jats:p>","DOI":"10.1093\/molbev\/msad020","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T10:36:46Z","timestamp":1675161406000},"source":"Crossref","is-referenced-by-count":17,"title":["Plasticity and Stereotypic Rewiring of the Transcriptome Upon Bacterial Evolution of Antibiotic Resistance"],"prefix":"10.1093","volume":"40","author":[{"given":"G\u00e1bor","family":"Gr\u00e9zal","sequence":"first","affiliation":[{"name":"HCEMM-BRC Metabolic Systems Biology Lab , Szeged , Hungary"},{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, E\u00f6tv\u00f6s Lor\u00e1nd Research Network , Szeged , Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9ka","family":"Spohn","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, E\u00f6tv\u00f6s Lor\u00e1nd Research Network , Szeged , Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya","family":"M\u00e9hi","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, E\u00f6tv\u00f6s Lor\u00e1nd Research Network , Szeged , Hungary"},{"name":"HCEMM-BRC Translational Microbiology Research Lab , Szeged , Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anett","family":"Dunai","sequence":"additional","affiliation":[{"name":"Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, E\u00f6tv\u00f6s Lor\u00e1nd Research Network , Szeged , 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