Mycobacterium tuberculosis PE25/PPE41 protein complex induces necrosis in macrophages: Role in virulence and disease reactivation?

Smanla Tundup; Krishnaveni Mohareer; Seyed E Hasnain

doi:10.1016/j.fob.2014.09.001

Mycobacterium tuberculosis PE25/PPE41 protein complex induces necrosis in macrophages: Role in virulence and disease reactivation?

FEBS Open Bio. 2014 Sep 16:4:822-8. doi: 10.1016/j.fob.2014.09.001. eCollection 2014.

Authors

Smanla Tundup¹, Krishnaveni Mohareer², Seyed E Hasnain³

Affiliations

¹ Department of Microbiology, University of Chicago, Chicago, IL, 60637, USA.
² Department of Biochemistry, School of Life Sciences, University of Hyderabad, Prof CR Rao Road, Hyderabad 500 046, India.
³ Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110 016, India ; Dr Reddy's Institute of Life Sciences, University of Hyderabad Campus, Prof CR Rao Road, Hyderabad 500046, India.

Abstract

Necrotic cell death during TB infection is an important prerequisite for bacterial dissemination and virulence. The underlying mechanisms and the bacterial factors involved therein are not well understood. The Mycobacterium tuberculosis (M. tuberculosis) co-operonic PE25/PPE41 protein complex, similar to ESAT-6/CFP-10, belonging to the PE/PPE and ESAT-6 families of genes has co-expanded and co-evolved in the genomes of pathogenic mycobacteria. We report a novel role of this highly immunogenic PE25/PPE41 protein complex in inducing necrosis, but not apoptosis, in macrophages. We propose that these protein complexes of M. tuberculosis, secreted by similar/unique transport system (Type VII), have an important role in M. tuberculosis virulence and disease reactivation.

Keywords: Mycobacterium; PE/PEE; PE25; PPE41; Rv2431; Tuberculosis.