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Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria

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Moon, Eun Chae, Modi, Tushar, Lee, Dong-yeon D., Yangaliev, Danis, Garcia-Ojalvo, Jordi, Ozkan, S. Banu, Süel, Gürol M.·2024·Science Advances
DOI 10.1126/sciadv.adq5249PMC PMC11567004
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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 Mg 2+ -dependent physiological cost. Coculture competition experiments show that Mg 2+ 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 Mg 2+ levels. Coarse-grained elastic-network modeling of ribosome conformational dynamics suggests that L22* ribosomes associate more tightly with Mg 2+ 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 Mg 2+ . Experiments confirmed a predicted ATP drop in L22* cells under Mg 2+ limitation, while WT cells were less affected. Intracellular competition for a finite Mg 2+ pool can thus suppress the establishment of an antibiotic-resistant ribosome variant.

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  • A coarse-grained elastic network model has been used to identify those sites with the greatest dynamic flexibility as candidates for the most labile cation binding sites.

    “As an alternative approach to infer the lability of ribosome-bound Mg2+ ions, a coarse-grained elastic network model has been used to identify those sites with the greatest dynamic flexibility as candidates for the most labile cation binding sites.69”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [69]

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Cited by

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Authors
Moon, E. C., Modi, T., Lee, D.-Y. D., Yangaliev, D., Garcia-Ojalvo, J., Ozkan, S. B., & Süel, G. M.
Affiliations
  • University of California San Diego (US)
  • Arizona State University (US)
  • Stanford University (US)
  • Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona Research Park, Barcelona 08003, Spain.
Corresponding author
Süel, Gürol M.
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2024-11-15
Volume
10
Issue
46
Pages
eadq5249-eadq5249
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.adq5249
PMC
PMC11567004
OpenAlex
W4404400194
Cited by
9
References
5
Citations by year
2026: 4 · 2025: 5
FWCI
1.16
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Advances (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Science Foundation (1715591)
  • Bill and Melinda Gates Foundation
  • Gordon and Betty Moore Foundation (1715591)
  • Ministerio de Ciencia, Innovación y Universidades
  • Generalitat de Catalunya
  • National Institute of General Medical Sciences (R35GM139645)
  • Division of Molecular and Cellular Biosciences (1715591)
  • Army Research Office (W911NF10361, W911NF-22-1-0107, W911NF)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
antibiotic resistance, magnesium limitation, Bacillus subtilis, ATP levels, ribosome abundance
MeSH terms
Adenosine Triphosphate, Anti-Bacterial Agents, Bacillus subtilis, Magnesium, Ribosomes, Drug Resistance, Bacterial

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