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Heterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair

Author

Listed:
  • Hollie J. Hindley

    (University of Edinburgh)

  • Zechuan Gong

    (Queen Mary University of London)

  • Shafagh Moradian

    (Queen Mary University of London)

  • Maria Grazia Giuliano

    (Queen Mary University of London
    Sant’anna School of Advanced Studies)

  • Andrei Sapelkin

    (Queen Mary University of London)

  • Ioly Kotta-Loizou

    (Imperial College London
    University of Hertfordshire)

  • Martin Buck

    (Imperial College London)

  • Christoph Engl

    (Queen Mary University of London)

  • Andrea Y. Weiße

    (University of Edinburgh
    University of Edinburgh)

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.

Suggested Citation

  • Hollie J. Hindley & Zechuan Gong & Shafagh Moradian & Maria Grazia Giuliano & Andrei Sapelkin & Ioly Kotta-Loizou & Martin Buck & Christoph Engl & Andrea Y. Weiße, 2025. "Heterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64759-3
    DOI: 10.1038/s41467-025-64759-3
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    1. Hollie J. Hindley & Zechuan Gong & Shafagh Moradian & Maria Grazia Giuliano & Andrei Sapelkin & Ioly Kotta-Loizou & Martin Buck & Christoph Engl & Andrea Y. Weiße, 2025. "Heterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
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    1. Hollie J. Hindley & Zechuan Gong & Shafagh Moradian & Maria Grazia Giuliano & Andrei Sapelkin & Ioly Kotta-Loizou & Martin Buck & Christoph Engl & Andrea Y. Weiße, 2025. "Heterogeneity in responses to ribosome-targeting antibiotics mediated by bacterial RNA repair," Nature Communications, Nature, vol. 16(1), pages 1-15, December.

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