Heterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair
- Hollie J. Hindley
- Zechuan Gong
- Shafagh Moradian
- Maria Grazia Giuliano
- Andrei Sapelkin
- Ioly Kotta-Loizou
- Martin Buck
- Christoph Engl
- Andrea Y. Weiße
2025-11-11
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.