Grézal, Gábor and Spohn, Réka and Méhi, Orsolya Katinka and Dunai, Anett and Lázár, Viktória and Bálint, Balázs and Nagy, István and Pál, Csaba and Papp, Balázs (2023) Plasticity and stereotypic rewiring of the transcriptome upon bacterial evolution of antibiotic resistance. MOLECULAR BIOLOGY AND EVOLUTION, 40 (2). No-msad020. ISSN 0737-4038
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Abstract
Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. 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.
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| Additional Information: | Funding Agency and Grant Number: Lendulet program of the Hungarian Academy of Sciences [LP-2009-013/2012, LP-2012-32/2018]; ELKH Lenduelet program [LP-2017-2010/2020]; Wellcome Trust WT [098016/Z/11/Z]; European Research Council [648364, 862077]; National Research, Development and Innovation Office; Ministry for Innovation and Technology [KKP KH125616, 126506, RRF-2.3.1-21-2022-00006, GINOP-2.3.2-15-2016-00026, GINOP-2.3.2-15-2 016-00014, GINOP-2.3.2-15-2 016-00020]; National Laboratory of Biotechnology Grant [2022-2.1.1-NL-2022-00008]; European Union [739593]; NKFIH [FK124254]; Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences [BO/608/21] Funding text: This work was supported by the "Lendulet" program of the Hungarian Academy of Sciences LP-2009-013/2012 (B.P.), LP-2012-32/2018 (C.P.), the ELKH Lenduelet program LP-2017-2010/2020 (C.P.), the Wellcome Trust WT 098016/Z/11/Z (B.P.), The European Research Council H2020-ERC-2014-CoG 648364-Resistance Evolution (C.P.), and H2020-ERC-2019-PoC 862077-Aware (C.P.), the National Research, Development and Innovation Office and the Ministry for Innovation and Technology under the "Frontline" program KKP KH125616 and 126506 (B.P. and C.P.), RRF-2.3.1-21-2022-00006 (B.P.), GINOP-2.3.2-15-2016-00026 (iChamber, B.P.), GINOP-2.3.2-15-2 016-00014 (EVOMER, C.P. and B.P.), GINOP-2.3.2-15-2 016-00020 (MolMedEx TUMORDNS, C.P.), National Laboratory of Biotechnology Grant 2022-2.1.1-NL-2022-00008 (C.P. and B.P.), The European Union's Horizon 202 0 research and innovation program under grant agreement No 739593 (B.P.). NKFIH grant FK124254 (O.M.), the Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences BO/608/21 (R.S.). |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 25 Sep 2023 11:41 |
| Last Modified: | 25 Sep 2023 11:41 |
| URI: | http://real.mtak.hu/id/eprint/174814 |
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