Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria
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- dc.contributor.author Moon, Eun Chae
- dc.contributor.author Modi, Tushar
- dc.contributor.author Lee, Dong-yeon D.
- dc.contributor.author Yangaliev, Danis
- dc.contributor.author García Ojalvo, Jordi
- dc.contributor.author Ozkan, S. Banu
- dc.contributor.author Süel, Gürol M.
- dc.date.accessioned 2024-11-18T15:14:12Z
- dc.date.available 2024-11-18T15:14:12Z
- dc.date.issued 2024
- dc.description.abstract Antibiotic-resistant ribosome variants arise spontaneously in bacterial populations; however, their impact on the overall bacterial physiology remains unclear. We studied the naturally arising antibiotic-resistant L22* ribosome variant of Bacillus subtilis and identified a Mg2+-dependent physiological cost. Coculture competition experiments show that Mg2+ limitation hinders the growth of the L22* variant more than the wild type (WT), even under antibiotic pressure. This growth disadvantage of L22* cells is not due to lower ribosome abundance but rather due to reduced intracellular Mg2+ levels. Coarse-grained elastic-network modeling of ribosome conformational dynamics suggests that L22* ribosomes associate more tightly with Mg2+ when compared to WT. We combined the structural modeling and experimental measurements in a steady-state model to predict cellular adenosine 5'-triphosphate (ATP) levels, which also depend on Mg2+. Experiments confirmed a predicted ATP drop in L22* cells under Mg2+ limitation, while WT cells were less affected. Intracellular competition for a finite Mg2+ pool can thus suppress the establishment of an antibiotic-resistant ribosome variant.
- dc.description.sponsorship This work was supported by the National Institute of General Medical Sciences [grant R35 GM139645 (G.M.S.)]; Army Research Office [grants W911NF-22-1-0107 and W911NF-1-0361 (G.M.S.)]; Bill & Melinda Gates Foundation INV-067331 (G.M.S.); Spanish Ministry of Science, Innovation and Universities and FEDER projects PID2021-127311NB-I00 and CEX2018-000792-M (J.G.-O.); Generalitat de Catalunya ICREA Academia program (J.G.-O.); National Science Foundation Division of Molecular and Cellular Biosciences [award 1715591 (S.B.O.)]; and Gordon and Betty Moore Foundation (S.B.O.).
- dc.format.mimetype application/pdf
- dc.identifier.citation Moon EC, Modi T, Lee DD, Yangaliev D, Garcia-Ojalvo J, Ozkan SB, et al. Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria. Sci Adv. 2024 Nov 15;10(46):eadq5249. DOI: 10.1126/sciadv.adq5249
- dc.identifier.doi http://dx.doi.org/10.1126/sciadv.adq5249
- dc.identifier.issn 2375-2548
- dc.identifier.uri http://hdl.handle.net/10230/68728
- dc.language.iso eng
- dc.publisher American Association for the Advancement of Science (AAAS)
- dc.relation.ispartof Sci Adv. 2024 Nov 15;10(46):eadq5249
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-127311NB-I00
- dc.rights Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Ribosomes
- dc.subject.other Antibiòtics
- dc.title Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion