Microbiology and Immunology

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

TitleDepleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death.
Publication TypeJournal Article
Year of Publication2017
AuthorsBotella L, Vaubourgeix J, Livny J, Schnappinger D
JournalNat Commun
Volume8
Pagination14731
Date Published2017 03 28
ISSN2041-1723
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.

DOI10.1038/ncomms14731
Alternate JournalNat Commun
PubMed ID28348398
PubMed Central IDPMC5379054
Grant ListU19 AI111143 / AI / NIAID NIH HHS / United States

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