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PPE38 modulates the innate immune response and is required for Mycobacterium marinum virulence

Dandan Dong1, Decheng Wang, Ming Li

  • 1Key Laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.

Infection and Immunity
|November 1, 2011
PubMed

Insights

The proline-proline-glutamic acid 38 (PPE38) protein is crucial for Mycobacterium marinum virulence. Its absence impairs cell surface properties, motility, biofilm formation, and host immune response, reducing disease severity.

Area of Science:

  • Microbiology
  • Immunology
  • Pathogenesis

Background:

  • Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) proteins are abundant in pathogenic mycobacteria.
  • The functions of most PE/PPE proteins, including PPE38, are largely uncharacterized.
  • Understanding these proteins is vital for deciphering mycobacterial pathogenesis.

Purpose of the Study:

  • To investigate the function of the PPE38 protein in Mycobacterium marinum.
  • To characterize the phenotypic changes in a PPE38-deficient mutant.
  • To elucidate PPE38's role in virulence and host-pathogen interactions.

Main Methods:

  • Isolation and characterization of a transposon-inactivated PPE38 mutant in Mycobacterium marinum.
  • Assessment of cell wall association and surface exposure of PPE38.
  • Phenotypic analysis including cord formation, motility, biofilm formation, and macrophage phagocytosis.
  • Evaluation of virulence in an adult zebrafish model and cytokine induction in macrophages.

Main Results:

  • PPE38 is localized to the cell wall and exposed on the bacterial surface.
  • PPE38 inactivation resulted in altered cell surface properties, reduced cord formation, sliding motility, and biofilm formation.
  • The PPE38 mutant showed impaired phagocytosis by macrophages and decreased virulence in zebrafish.
  • PPE38 influences the induction of proinflammatory cytokines in infected macrophages.

Conclusions:

  • PPE38 is a novel virulence factor in Mycobacterium marinum.
  • PPE38 contributes to mycobacterial pathogenesis by modulating bacterial surface characteristics and host innate immune responses.
  • Targeting PPE38 could be a potential strategy for controlling mycobacterial infections.

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