Mycobacterium marinum Erp is a virulence determinant required for cell wall integrity and intracellular survival

Christine L Cosma1, Kathryn Klein, Rosa Kim

  • 1Department of Microbiology, University of Washington, Seattle, WA 98195, USA. ccosma@washington.edu

Insights

Mycobacterium tuberculosis exported repetitive protein (Erp) is crucial for virulence. Erp-deficient Mycobacterium marinum showed impaired growth and survival in macrophages, indicating Erp

Area of Science:

  • Microbiology
  • Pathogenesis
  • Immunology

Background:

  • The Mycobacterium tuberculosis exported repetitive protein (Erp) is a known virulence factor.
  • Erp is essential for M. tuberculosis growth in macrophages and in vivo.
  • Understanding Erp's role in pathogenesis is key to developing new treatments.

Purpose of the Study:

  • To investigate the function of the Erp homologue in Mycobacterium marinum.
  • To determine the specific stage of infection where Erp is required.
  • To compare the virulence mechanisms of Erp-deficient and RD1-deficient M. marinum.

Main Methods:

  • Generated an erp-deficient mutant of Mycobacterium marinum.
  • Assessed bacterial growth and survival in cultured macrophages.
  • Utilized a zebrafish embryo infection model for real-time visualization of infection dynamics.
  • Compared the erp-deficient mutant with a previously characterized DeltaRD1 mutant.

Main Results:

  • Erp-deficient M. marinum exhibited attenuated growth in macrophages and reduced virulence in leopard frogs.
  • In zebrafish embryos, Erp-deficient bacteria failed to grow and survive early after phagocytosis by macrophages.
  • DeltaRD1 mutant bacteria showed normal macrophage growth but impaired cell-to-cell spread.
  • Erp-deficient bacteria displayed in vitro permeability defects, unlike RD1-deficient bacteria.

Conclusions:

  • Erp is essential for both M. tuberculosis and M. marinum virulence.
  • Erp is required for early-stage intracellular survival of mycobacteria within macrophages.
  • Erp likely contributes to virulence by maintaining bacterial membrane integrity.

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