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Cell wall and immune modulation by Rv1800 (PPE28) helps M. smegmatis to evade intracellular killing

Pradeep Kumar Anand1, Varinder Saini2, Jasbinder Kaur3

  • 1Department of Biotechnology, BMS Block-1, South Campus, Panjab University, Chandigarh, 160014, India.

International Journal of Biological Macromolecules
|July 16, 2023
PubMed

Insights

The Rv1800 protein from pathogenic mycobacteria exhibits esterase activity and enhances bacterial survival under stress. Its N-terminus aids thermostability and transport, while the C-terminus shows enzymatic function, impacting immune responses.

Area of Science:

  • Microbiology
  • Protein Biochemistry
  • Immunology

Background:

  • Rv1800 is a PPE family protein exclusively found in pathogenic mycobacteria.
  • Its expression is induced in Mycobacterium tuberculosis under acidic stress conditions.

Purpose of the Study:

  • To characterize the functional domains and biochemical activities of the Rv1800 protein.
  • To investigate the role of Rv1800 in mycobacterial stress resistance and host-pathogen interactions.

Main Methods:

  • In-silico analysis to predict protein domains and activity.
  • Biochemical assays to determine esterase activity of Rv1800 and its domains.
  • Expression of Rv1800 in Mycobacterium smegmatis to assess phenotypic changes and stress resistance.
  • Macrophage infection assays to evaluate intracellular survival and immune responses.

Main Results:

  • The C-terminus of Rv1800 possesses esterase activity, while the N-terminus contributes to thermostability and protein transport.
  • Rv1800 expression in M. smegmatis conferred resistance to various stresses and increased lipid content.
  • Rv1800 facilitated higher intracellular survival of macrophages and modulated immune responses, reducing pro-inflammatory cytokines.

Conclusions:

  • Rv1800 exhibits dual functionality with esterase activity in the C-terminus and structural roles in the N-terminus.
  • Rv1800 plays a significant role in modulating host immune responses and lipid metabolism, supporting mycobacterial survival.
  • Rv1800 and its domains show potential as targets for antibody-mediated immunity against tuberculosis.
Keywords:
Cell wall modulationImmune modulationInfectionIntracellular survivalMycobacterium tuberculosis

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