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In silico characterization of a putative ORF-MAP1138c of Mycobacterium avium subspecies paratuberculosis(MAP) with its implications in virulence
© Hassan et al; licensee BioMed Central Ltd. 2014
- Published: 2 April 2014
- Immune Evasion
- Mycobacterial Infection
- Mycobacterium Avium Complex
- Mycobacterium Avium Subspecies Paratuberculosis
- Host Macrophage
Johne’s disease is a chronic mycobacterial infection of the small intestine affecting ruminants worldwide. It is estimated that over 50% of the European Union (EU) dairy holdings is infected . The causal agent is Mycobacterium avium subspecies paratuberculosis (MAP), a slow-growing, acid-fast bacterium. It is a part of the Mycobacterium avium complex (MAC), which also comprises of opportunistic pathogens of humans, as well as innocuous, environmental bacteria . MAP generally interacts with macrophages via different types of receptors, including Toll-like receptors (TLRs) [3, 4]. It has been demonstrated of late that H37Rv1411c (LprG) enhances the recognition of triacylated Mycobacterium tuberculosis glycolipids by TLR2 and thereby restraining the expression of MHC-II molecules and processing of antigen and presentation of MHC restricted antigens by macrophages in a TLR2-dependent manner [5, 6]. However, little is known about how M. paratuberculosis evades and resists this active CD4+ T-cell response and survives and infects other macrophages, a hallmark of mycobacterial infections. In this context, the identification of antigenic proteins is useful in understanding the immune evasion mechanism of MAP within host macrophages.
In this study, a comparative proteomic analysis of an orthologous putative gene MAP1138c or LprG and H37Rv1411c (LprG) was done using online bioinformatics tools namely ProtPram and SignalP 4.1, Phosphor 2.1, ProtScan and Hydropathy plot. The theoretical 3D structure of MAP1138c was generated using SWISS MODEL server using H37Rv1411c (LprG) as template. The secondary and super secondary structures of MAP1138c protein were identified and analyzed using PROMOTIF. The theoretical 3D structure generated was further assessed for its reliability using QMEAN, ANOLEA and GROMOS structure assessment tools of SWISS MODEL server.
A comparative study of the physiochemical parameters of MAP1138c and H37Rv1411c (LprG) (*GRAVY (-ve) = hydrophilic nature and (+ve) = hydrophobic nature
Molecular weight (kD)
Amino acid composition
Instability Index ( > 40 = unstable)
Grand Average of Hydropathicity (GRAVY)*
Through our comprehensive in silico analysis of MAP1138c, we identified several key aspects fundamentally important to propose a function for this putative protein. These studies reflect upon the possible role of MAP1138c in inhibiting MHC-II Ag processing leading to reduced recognition of infected macrophages by CD4+ T cells. This may be an important mechanism for immune evasion during persistent M. paratuberculosis infection in ruminants and humans.
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