Mycobacterium tuberculosis PE31 (Rv3477) Attenuates Host Cell Apoptosis and Promotes Recombinant M. smegmatis Intracellular Survival via Up-regulating GTPase Guanylate Binding Protein-1

Abstract

The Mycobacterium (M.) tuberculosis comprising proline-glutamic acid (PE) subfamily proteins associate with virulence, pathogenesis, and host-immune modulations. While the functions of most of this family members are not yet explored. Here, we explore the functions of "PE only" subfamily member PE31 (Rv3477) in virulence and host-pathogen interactions. We have expressed the M. tuberculosis PE31 in non-pathogenic Mycobacterium smegmatis strain (Ms_PE31) and demonstrated that PE31 significantly altered the cell facet features including colony morphology and biofilm formation. PE31 expressing M. smegmatis showed more resistant to the low pH, diamide, H 2 O 2 and surface stress. Moreover, Ms_PE31 showed higher intracellular survival in macrophage THP-1 cells. Ms_PE31 significantly down-regulated the production of IL-12p40 and IL-6, while up-regulates the production of IL-10 in macrophages. Ms_PE31 also induced the expression of guanylate-binding protein-1 (GBP-1) in macrophages. Further analysis demonstrates that Ms_PE31 inhibits the caspase-3 activation and reduces the macrophages apoptosis. Besides, the NF-κB signaling pathway involves the interplay between Ms_PE31 and macrophages. Collectively, our finding identified that PE31 act as a functionally relevant virulence factor of M. tuberculosis.

An Integrative Network Approach to Identify Common Genes for the Therapeutics in Tuberculosis and Its Overlapping Non-Communicable Diseases

“…It has been reported that Mycobacterium tuberculosis inhibits caspase-3 leading to a reduction in macrophages apoptosis (Ali et al, 2020). Increased level of CD4+CD25+FOXP3+ T regulatory cells has been reported in Crohn's disease and intestinal tuberculosis patients.…”

Role of the PE/PPE Family in Host–Pathogen Interactions and Prospects for Anti-Tuberculosis Vaccine and Diagnostic Tool Design

“…Conversely, PE_PGRS62 ( Long et al, 2019 ) and PE_PGRS18 ( Yang W. et al, 2017 ) can decrease apoptosis and enhance survival rate. PE31 increased guanylate-binding protein-1 (GBP-1) expression and inhibited caspase-3 activation and macrophage apoptosis through the NF-κB pathway ( Ali et al, 2020 ). Although apoptosis caused by some bacterial proteins favors bacterial survival, it also helps to kill intracellular bacteria and activate adaptive immunity ( Schaible et al, 2003 ; Srinivasan et al, 2014 ).…”

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