creators_name: Bansal, Roohi
creators_name: Anil Kumar, Vijjamarri
creators_name: Sevalkar, Ritesh Rajesh
creators_name: Singh, Prabhat Ranjan
creators_name: Sarkar, Dibyendu
type: article
datestamp: 2018-03-26 10:52:13
lastmod: 2018-03-26 10:52:13
metadata_visibility: show
title: Mycobacterium tuberculosis virulence-regulator PhoP interacts with alternative sigma factor SigE during acid-stress response
ispublished: pub
subjects: QR
keywords: Bacterial Proteins/genetics*
Bacterial Proteins/metabolism
Gene Expression Regulation, Bacterial
Hydrogen-Ion Concentration
note: Copyright of this article belongs Blackwell Scientific Publications.
abstract: The ability to sense acid stress and mount an appropriate adaptive response by Mycobacterium tuberculosis, which adapts a long-term residence in the macrophage phagosome, remains one of the critical features that defines mycobacterial physiology and its intracellular location. To understand the mechanistic basis of adaptation of the intracellular pathogen, we studied global regulation of M. tuberculosis gene expression in response to acid stress. Although recent studies indicate a role for the virulence-associated phoP locus in pH-driven adaptation, in this study, we discovered a strikingly novel regulatory mechanism, which controls acid-stress homeostasis. Using mycobacterial protein fragment complementation and in vitro interaction analyses, we demonstrate that PhoP interacts with acid-inducible extracytoplasmic SigE (one of the 13 M. tuberculosis sigma factors) to regulate a complex transcriptional program. Based on these results, we propose a model to suggest that PhoP-SigE interaction represents a major requirement for the global acid stress response, absence of which leads to strongly reduced survival of the bacilli under acidic pH conditions. These results account for the significant growth attenuation of the phoP mutant in both cellular and animal models, and unravel the underlying global mechanism of how PhoP induces an adaptive program in response to acid stress.
date: 2017
date_type: published
publication: Molecular Microbiology
volume: 104
number: 3
publisher: Blackwell Scientific Publications
pagerange: 400-411
id_number: doi:10.1111/mmi.13635
refereed: TRUE
issn: 0950382X
official_url: http://dx.doi.org/10.1111/mmi.13635
citation:   Bansal, Roohi and Anil Kumar, Vijjamarri and Sevalkar, Ritesh Rajesh and Singh, Prabhat Ranjan and Sarkar, Dibyendu  (2017) Mycobacterium tuberculosis virulence-regulator PhoP interacts with alternative sigma factor SigE during acid-stress response.  Molecular Microbiology, 104 (3).  pp. 400-411.  ISSN 0950382X