Identification of a Transcription Factor That Regulates Host Cell Exit and Virulence of Mycobacterium tuberculosis

The interaction of Mycobacterium tuberculosis (Mtb) with host cell death signaling pathways is characterized by an initial anti-apoptotic phase followed by a pro-necrotic phase to allow for host cell exit of the bacteria. The bacterial modulators regulating necrosis induction are poorly understood....

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Published in:PLoS pathogens 2016-05, Vol.12 (5), p.e1005652-e1005652
Main Authors: Srinivasan, Lalitha, Gurses, Serdar A, Hurley, Benjamin E, Miller, Jessica L, Karakousis, Petros C, Briken, Volker
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Autophagy
Bacteria
Bacterial Proteins - metabolism
Biology and Life Sciences
Cells (Biology)
Disease Models, Animal
Experiments
Flow cytometry
Gangrene
Genetic aspects
Guinea Pigs
Health aspects
Immunoblotting
Infections
Kinases
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy
Microscopy, Electron, Transmission
Mycobacterium tuberculosis
Mycobacterium tuberculosis - pathogenicity
Pathogens
Polymerase Chain Reaction
Research and Analysis Methods
Signal transduction
Transcription factors
Transcription Factors - metabolism
Tuberculosis
Tuberculosis - metabolism
Virulence (Microbiology)
Virulence - physiology
Virulence Factors - metabolism
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description The interaction of Mycobacterium tuberculosis (Mtb) with host cell death signaling pathways is characterized by an initial anti-apoptotic phase followed by a pro-necrotic phase to allow for host cell exit of the bacteria. The bacterial modulators regulating necrosis induction are poorly understood. Here we describe the identification of a transcriptional repressor, Rv3167c responsible for regulating the escape of Mtb from the phagosome. Increased cytosolic localization of MtbΔRv3167c was accompanied by elevated levels of mitochondrial reactive oxygen species and reduced activation of the protein kinase Akt, and these events were critical for the induction of host cell necrosis and macroautophagy. The increase in necrosis led to an increase in bacterial virulence as reflected in higher bacterial burden and reduced survival of mice infected with MtbΔRv3167c. The regulon of Rv3167c thus contains the bacterial mediators involved in escape from the phagosome and host cell necrosis induction, both of which are crucial steps in the intracellular lifecycle and virulence of Mtb.
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subjects Animals
Apoptosis
Autophagy
Bacteria
Bacterial Proteins - metabolism
Biology and Life Sciences
Cells (Biology)
Disease Models, Animal
Experiments
Flow cytometry
Gangrene
Genetic aspects
Guinea Pigs
Health aspects
Immunoblotting
Infections
Kinases
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy
Microscopy, Electron, Transmission
Mycobacterium tuberculosis
Mycobacterium tuberculosis - pathogenicity
Pathogens
Polymerase Chain Reaction
Research and Analysis Methods
Signal transduction
Transcription factors
Transcription Factors - metabolism
Tuberculosis
Tuberculosis - metabolism
Virulence (Microbiology)
Virulence - physiology
Virulence Factors - metabolism
title Identification of a Transcription Factor That Regulates Host Cell Exit and Virulence of Mycobacterium tuberculosis
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