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Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in Mycobacterium marinum

Yuchen Wang1,2, Yuting Tang3, Chen Lin3

  • 1Department of Microbiology, School of Life Science, Fudan University, Shanghai 200090, China.

Iscience
|January 10, 2022
PubMed

Insights

The progenitor type VII secretion system (T7SS) in Mycobacterium marinum, ESX-4, does not secrete its own substrates. However, its disruption enhances secretion by other T7SS systems, impacting host cell interactions.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Pathogenesis

Background:

  • The type VII secretion system (T7SS) is crucial for Mycobacterium tuberculosis pathogenesis, mediating the secretion of Esx, Esp, and PE/PPE proteins.
  • Five T7SS subtypes (ESX-1 to ESX-5) exist in M. tuberculosis, with ESX-4 being the ancestral system, yet its function remains largely unknown.

Purpose of the Study:

  • To investigate the function of the ESX-4 secretion system in Mycobacterium marinum.
  • To elucidate the relationship between the ancestral ESX-4 and other T7SS subtypes in mycobacteria.

Main Methods:

  • Investigated ESX-4 substrate secretion in Mycobacterium marinum under tested conditions.
  • Generated and analyzed an eccC4 deletion mutant (ΔeccC4) to assess its impact on T7SS activity.
  • Evaluated the mutant's efficiency in inducing actin cytoskeleton rearrangement and phagocytosis by macrophages.

Main Results:

  • ESX-4 in M. marinum failed to secrete its cognate substrates, EsxT and EsxU, under the tested conditions.
  • Deletion of eccC4, an essential ESX-4 component, led to increased secretion of ESX-1 and ESX-5 substrates.
  • The ΔeccC4 mutant exhibited enhanced actin cytoskeleton rearrangement and increased phagocytosis by macrophages.

Conclusions:

  • Reveals a previously unrecognized crosstalk between the progenitor ESX-4 and other T7SS systems in mycobacteria.
  • Provides novel insights into the evolutionary dynamics and functional interplay of T7SS subtypes.
  • Suggests a regulatory role for ESX-4 in modulating the activity of other T7SSs, influencing host-pathogen interactions.
Keywords:
MicrobiologyMolecular biology

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