Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death. 2017

Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
Department of Microbiology and Immunology, Weill Cornell Medicine, 413E 69th Street, New York, New York 10021, USA.

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.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D005260 Female Females
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D012234 Rho Factor A protein which effects termination of RNA synthesis during the genetic transcription process by dissociating the ternary transcription complex RNA;-RNA POLYMERASE DNA at the termination of a gene. E Coli Transcription Termination Factor,Factor, Rho
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D014376 Tuberculosis Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM TUBERCULOSIS. Koch's Disease,Kochs Disease,Mycobacterium tuberculosis Infection,Infection, Mycobacterium tuberculosis,Infections, Mycobacterium tuberculosis,Koch Disease,Mycobacterium tuberculosis Infections,Tuberculoses

Related Publications

Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
January 2015, Methods in molecular biology (Clifton, N.J.),
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
July 2015, Nucleic acids research,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
February 2022, Communications biology,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
June 2006, Molecular cell,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
March 2023, Drug discovery today,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
July 2017, PLoS genetics,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
April 2023, iScience,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
April 1985, Journal of molecular biology,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
January 1996, The Journal of biological chemistry,
Laure Botella, and Julien Vaubourgeix, and Jonathan Livny, and Dirk Schnappinger
February 1980, European journal of biochemistry,
Copied contents to your clipboard!