Abstract
Background: Protein phosphorylation and dephosphorylation play indispensable roles in the biology of infection. Mycobacterium tuberculosis (Mtb) secretes two protein-tyrosine phosphatases namely PtpA and PtpB. PtpB is a triple-specificity phosphatase which plays role in survival of mycobacteria within the host. Owing to its secretory nature, it could be an attractive drug target for TB drugs.
Objective: Since, very limited reports are available on the functional roles of PtpB; we in the present study have addressed the mechanism of this phosphatase through a series of experiments, where we have shown that during growth and intracellular survival PtpB regulates several proteins of Mtb and the macrophage.
Methods: To study the regulatory effect of PtpB in the host, we have transiently expressed ptpB in J774A.1 macrophage cell line. The transfected cell lysates were further subjected to 2D gel electrophoresis and the differentially expressed proteins were identified by Mass spectrometry.
Results and Conclusion: The proteomic data shows upregulation of a number of chaperone proteins like hsp75, hsp 70, BiP, mortalin suggesting the possible role of PtpB in regulating the stress conditions within the host to promote mycobacterial survival. Cytoskeleton binding proteins (like coronin-1, profilin-1) were also found to be upregulated showing its probable role in blocking phagosome-lysosome fusion. Its antigenic nature was confirmed by showing its presence in TB-patient sera by western blotting. Our results suggest that PtpB is secreted by mycobacteria during infection which alters host proteins in a number of ways to enhance the survival of mycobacteria inside the host.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA4592.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019
