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Moonlighting by PPE2 Protein: Focus on Mycobacterial Virulence

Ravi Pal1,2, Sudip Ghosh3, Sangita Mukhopadhyay4

  • 1Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics, Uppal, Hyderabad, Telangana, India.

Journal of Immunology (Baltimore, Md. : 1950)
|November 9, 2021
PubMed

Insights

Tuberculosis protein PPE2 disrupts the immune system and aids bacterial survival. Targeting PPE2 offers a promising new strategy for developing effective tuberculosis therapeutics.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • The proline-glutamic acid and proline-proline-glutamic acid (PPE) family of proteins constitutes a significant portion of the Mycobacterium tuberculosis genome.
  • Some PPE proteins are recognized as critical factors in mycobacterial virulence.

Purpose of the Study:

  • To investigate the role of PPE2 (Rv0256c) in tuberculosis pathogenesis.
  • To evaluate PPE2 as a potential therapeutic target against tuberculosis.

Main Methods:

  • Analysis of PPE2's unique structural features, including its nuclear localization signal, DNA binding domain, and SRC homology 3 (PXXP) binding domain.
  • Investigation of PPE2's impact on host innate immune responses, such as nitric oxide (NO) and reactive oxygen species (ROS) production, and myeloid hematopoiesis.
  • Characterization of PPE2 as a secreted protein expressed during active tuberculosis infection.

Main Results:

  • PPE2 was found to possess pleiotropic effects, significantly weakening the innate immune system.
  • PPE2 interferes with host immune mechanisms through its unique structural domains.
  • PPE2 is a secreted protein crucial for the survival of M. tuberculosis during active infection.

Conclusions:

  • PPE2 plays a multifaceted role in tuberculosis pathogenesis by modulating the host immune response and promoting bacterial survival.
  • PPE2 represents a novel and valuable drug target for the development of innovative anti-tuberculosis therapies.

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