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Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death

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  • Laure Botella

    (Weill Cornell Medicine)

  • Julien Vaubourgeix

    (Weill Cornell Medicine)

  • Jonathan Livny

    (Broad Institute of MIT and Harvard)

  • Dirk Schnappinger

    (Weill Cornell Medicine)

Abstract

Rifampicin, which inhibits bacterial RNA polymerase, provides one of the most effective treatments for tuberculosis. Inhibition of the transcription termination factor Rho is used to treat some bacterial infections, but its importance varies across bacteria. Here we show that Rho of Mycobacterium tuberculosis functions to both define the 3′ ends of mRNAs and silence substantial fragments of the genome. Brief inactivation of Rho affects over 500 transcripts enriched for genes of foreign DNA elements and bacterial virulence factors. Prolonged inactivation of Rho causes extensive pervasive transcription, a genome-wide increase in antisense transcripts, and a rapid loss of viability of replicating and non-replicating M. tuberculosis in vitro and during acute and chronic infection in mice. Collectively, these data suggest that inhibition of Rho may provide an alternative strategy to treat tuberculosis with an efficacy similar to inhibition of RNA polymerase.

Suggested Citation

  • Laure Botella & Julien Vaubourgeix & Jonathan Livny & Dirk Schnappinger, 2017. "Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14731
    DOI: 10.1038/ncomms14731
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    Cited by:

    1. Britney Martinez & Binod K. Bharati & Vitaly Epshtein & Evgeny Nudler, 2022. "Pervasive Transcription-coupled DNA repair in E. coli," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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