The Multifunctional PE_PGRS11 Protein from Mycobacterium tuberculosis Plays a Role in Regulating Resistance to Oxidative Stress

Chaturvedi, Rashmi and Bansal, Kushagra and Narayana, Yeddula and Kapoor, Nisha and Sukumar, Namineni and Togarsimalemath, Shambhuprasad Kotresh and Chandra, Nagasuma R and Mishra, Saurabh and Ajitkumar, Parthasarathi and Joshi, Beenu and Katoch, Vishwa Mohan and Patil, Shripad A and Balaji, Kithiganahalli N (2010) The Multifunctional PE_PGRS11 Protein from Mycobacterium tuberculosis Plays a Role in Regulating Resistance to Oxidative Stress. In: Journal of Biological Chemistry, 285 (40). pp. 30389-30403.

PDF from.pdf - Published Version Restricted to Registered users only Download (2MB) | Request a copy

Abstract

Mycobacterium tuberculosis utilizes unique strategies to survive amid the hostile environment of infected host cells. Infection-specific expression of a unique mycobacterial cell surface antigen that could modulate key signaling cascades can act as a key survival strategy in curtailing host effector responses like oxidative stress. We demonstrate here that hypothetical PE_PGRS11 ORF encodes a functional phosphoglycerate mutase. The transcriptional analysis revealed that PE_PGRS11 is a hypoxia-responsive gene, and enforced expression of PE_PGRS11 by recombinant adenovirus or Mycobacterium smegmatis imparted resistance to alveolar epithelial cells against oxidative stress. PE_PGRS11-induced resistance to oxidative stress necessitated the modulation of genetic signatures like induced expression of Bcl2 or COX-2. This modulation of specific antiapoptotic molecular signatures involved recognition of PE_PGRS11 by TLR2 and subsequent activation of the PI3K-ERK1/ 2-NF-kappa B signaling axis. Furthermore, PE_PGRS11 markedly diminished H2O2-induced p38 MAPK activation. Interestingly, PE_PGRS11 protein was exposed at the mycobacterial cell surface and was involved in survival of mycobacteria under oxidative stress. Furthermore, PE_PGRS11 displayed differential B cell responses during tuberculosis infection. Taken together, our investigation identified PE_PGRS11 as an in vivo expressed immunodominant antigen that plays a crucial role in modulating cellular life span restrictions imposed during oxidative stress by triggering TLR2-dependent expression of COX-2 and Bcl2. These observations clearly provide a mechanistic basis for the rescue of pathogenic Mycobacterium-infected lung epithelial cells from oxidative stress.

Item Type:	Journal Article
Publication:	Journal of Biological Chemistry
Publisher:	The American Society for Biochemistry and Molecular Biology
Additional Information:	Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Interdisciplinary Sciences > Supercomputer Education & Research Centre
Date Deposited:	21 Oct 2010 05:13
Last Modified:	21 Oct 2010 05:13
URI:	http://eprints.iisc.ac.in/id/eprint/33271

Actions (login required)

View Item