Heterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
RNA repair is critical for cellular function. The Rtc system maintains RNA integrity within the translational machinery of bacteria. In E. coli, Rtc expression enables cells to rescue growth and survive treatment by conferring transient resistance to ribosome-targeting antibiotics, yet the mechanisms underpinning this resistance remain obscure. Here, we present a computational model of Rtc-regulated repair of translational RNAs. Integrating model predictions with experimental validations, we uncover notable cell-to-cell heterogeneity in rtc expression that impacts on translational capacity, indicating that rtc may induce a form of heteroresistance. We moreover identify Rtc targets that may reduce the translational capacity of cells and so potentiate antibiotic effects. Our findings elucidate a complex response underpinning resistance conferred by Rtc, offering alternate routes for addressing resistance in E. coli and other relevant pathogens.
Date Issued
2025-11-11
Date Acceptance
2025-09-23
Citation
Nature Communications, 2025, 16
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
16
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41219221
PII: 10.1038/s41467-025-64759-3
Subjects
Ribosomes
Escherichia coli
Anti-Bacterial Agents
RNA, Bacterial
Protein Biosynthesis
Drug Resistance, Bacterial
Escherichia coli Proteins
Gene Expression Regulation, Bacterial
Publication Status
Published
Coverage Spatial
England
Article Number
9620
Date Publish Online
2025-11-11