title: Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death.
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.
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medicine, 413E 69th Street, New York, New York 10021, USA.
authors.forename: Laure
authors.initials: L
authors.lastname: Botella
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medicine, 413E 69th Street, New York, New York 10021, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Vaubourgeix
authors.affiliation: Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Livny
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medicine, 413E 69th Street, New York, New York 10021, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schnappinger
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D016680:Genome, Bacterial; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D011485:Protein Binding; D016372:RNA, Antisense / Q000235:genetics; D012234:Rho Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome / Q000235:genetics; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D016372:RNA, Antisense; D012234:Rho Factor; D000255:Adenosine Triphosphate