Cloning and characterization of a novel PE_PGRS60 protein (Rv3652) of Mycobacterium tuberculosis H₃₇Rv exhibit fibronectin‐binding property

Abstract

The binding of pathogenic bacteria to extracellular matrix components enhances adhesion and invasion of host cells. The host receptor proteins such as fibronectin (Fn) targeted to pathogenic ligands that have clinical importance. In the present study, we cloned, expressed, purified, and identified a novel Fn-binding protein from PE_PGRS60 (Rv3652) of Mycobacterium tuberculosis H37 Rv. The protein product of Rv3652 showed optimum binding efficiency to 10 ng Fn at 0.2 µg purified protein of PE_PGRS60 and 20 ng Fn at 0.2 µg concentrations, respectively. PE_PGRS60 protein (primary sequences) of different pathogenic mycobacterium species retrieved from NCBI exhibited complete homology at the 104 residues on multiple sequence alignment. The primary sequence of protein from H37 Rv was further used to predict cleavage signals. The secondary structure prediction method revealed a number of residues responsible for alpha helices formation and percentage of residues participating in the random coils and extended strands. In addition, online prediction tools such as B- and T-cell epitopes showed the surface probability scale and antigenic propensity scale. The current finding opens new opportunity to mycobacterial survival and pathogenesis research of PE-polymorphic GC-rich repetitive sequences (PE-PGRS) family proteins.

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

“…Recent reports revealed that PE11 knockdown strains could significantly enhance fibronectin attachment protein production, contributing to the attachment to the host extracellular matrix ( Rastogi et al, 2017 ). PE_PGRS60 can bind to fibronectin, which results in enhanced adhesion and invasion ( Meena and Meena, 2016 ).…”

Molecular Basis Underlying Host Immunity Subversion by Mycobacterium tuberculosis PE/PPE Family Molecules

“…The additional roles of PE/PPE protein are summarized. PE_PGRS60 (Rv3652) was a novel fibronectin-binding protein (Meena and Meena, 2016). PE_PGRS11, a potent phosphoglycerate mutase, mediates the immune invasion of bacteria to hypoxic conditions (Meena, 2015).…”

Adhesion molecules facilitate host-pathogen interaction & mediate Mycobacterium tuberculosis pathogenesis

“…FnBP complex constitutes antigen-85A, -85B, -85C (Ag85a, Ag85B, Ag85C) and FnBP A, B, C which play a crucial role in M. tuberculosis pathogenesis and also illustrate cell wall mycolyl transferase activity23. FnBPs mainly belong to proline glutamic polymorphic CG repetitive sequence family of genes present in mycobacteria242526. Previous studies have validated its binding to fibronectin (Fn), a multidomain glycoprotein on host surface22.…”