PE_PGRS62 promotes the survival of Mycobacterium smegmatis within macrophages via disrupting ER stress-mediated apoptosis

J Cell Physiol. 2019 Nov;234(11):19774-19784. doi: 10.1002/jcp.28577. Epub 2019 Apr 1.

Abstract

Mycobacterium tuberculosis, the leading causative agent of tuberculosis, remains one of the most deadly infectious pathogens. PE_PGRS proteins become a new focus as their species specificity in mycobacteria, especially in pathogenic mycobacteria. Despite intensive research, PE_PGRS proteins are still a mysterious aspect of mycobacterial pathogenesis with unknown mechanism. Herein, we focused on a PE_PGRS member from M. tuberculosis, PE_PGRS62, characterized by a surface-exposed protein function in disrupting phagolysosome maturation. Expression of PE_PGRS62 in Mycobacterium smegmatis, a nonpathogenic species naturally deficient in PE_PGRS genes, resulted in enhanced resistance to various in vitro stresses and cellular survival in macrophage. As a consequence, the cytokine profiles of macrophage were disturbed and cell apoptosis were inhibited via decreasing endoplasmic reticulum stress response.

Keywords: ER stress response; Mycobacterium tuberculosis; PE_PGRS62; apoptosis; macrophage; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Endoplasmic Reticulum Stress / genetics
  • Gene Expression Regulation, Bacterial / genetics
  • Humans
  • Macrophages / microbiology
  • Mycobacterium smegmatis / genetics*
  • Mycobacterium smegmatis / pathogenicity
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / pathogenicity
  • Phagosomes / genetics
  • Tuberculosis / genetics*
  • Tuberculosis / microbiology

Substances

  • Bacterial Proteins
  • PE-PGRS62 protein, Mycobacterium tuberculosis