Moon, Eun ChaeModi, TusharLee, Dong-yeon D.Yangaliev, DanisGarcía Ojalvo, JordiOzkan, S. BanuSüel, Gürol M.2024-11-182024-11-182024Moon 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.adq52492375-2548http://hdl.handle.net/10230/68728Antibiotic-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.application/pdfengCopyright © 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.RibosomesAntibiòticsinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/sciadv.adq5249info:eu-repo/semantics/openAccess