The PPE2 protein of Mycobacterium tuberculosis is secreted during infection and facilitates mycobacterial survival inside the host

Mycobacterium tuberculosis secrets various effector proteins to evade host immune responses for facilitating its intracellular survival. The bacterial genome encodes several unique PE/PPE family proteins, which have been implicated to play important role in mycobacterial pathogenesis. A member of th...

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Published in:Tuberculosis (Edinburgh, Scotland) Scotland), 2023-12, Vol.143, p.102421-102421, Article 102421
Main Authors: Bisht, Manoj Kumar, Pal, Ravi, Dahiya, Priyanka, Naz, Saba, Sanyal, Priyadarshini, Nandicoori, Vinay Kumar, Ghosh, Sudip, Mukhopadhyay, Sangita
Format: Article
Language:English
Subjects:
Animals
Antigens, Bacterial - metabolism
Bacterial Proteins - metabolism
Host-Pathogen Interactions
iNOS/NO
Intracellular survival
Macrophage
Mice
Mycobacterium smegmatis - genetics
Mycobacterium smegmatis - metabolism
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - pathogenicity
PPE2 protein of Mycobacterium tuberculosis
Tuberculosis - metabolism
Tuberculosis - microbiology
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Summary:Mycobacterium tuberculosis secrets various effector proteins to evade host immune responses for facilitating its intracellular survival. The bacterial genome encodes several unique PE/PPE family proteins, which have been implicated to play important role in mycobacterial pathogenesis. A member of this family, PPE2 have been shown to contain a monopartite nuclear localization signal (NLS) and a DNA binding domain. In this study, we demonstrate that PPE2 protein is present in the sera of mice infected with either M. smegmatis expressing PPE2 or a clinical strain of M. tuberculosis (CDC1551). It was found that exogenously added PPE2 can permeate through the macrophage cell membrane and eventually translocate into the nucleus which requires the presence of NLS which showed considerable homology to HIV-tat like cell permeable peptides. Exogenously added PPE2 could inhibit NO production and decreased mycobacterial survival in macrophages. PPE2-null mutant of M. tuberculosis failed to inhibit NO production and had poor survival in macrophages which could be rescued by complementation with full-length PPE2. PPE2-null mutants also had poor survival in the lungs of infected mice indicating that PPE2 even when present in the bloodstream can confer a survival advantage to mycobacteria.
ISSN:1472-9792
1873-281X
DOI:10.1016/j.tube.2023.102421