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Non-proteolytic functions of microbial proteases increase pathological complexity.

Veronica M Jarocki1, Jessica L Tacchi, Steven P Djordjevic

  • 1The ithree institute, Proteomics Core Facility, University of Technology, Sydney, NSW, Australia.

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|December 11, 2014
PubMed
Summary

Microbial proteases have dual roles, acting as virulence factors and performing non-proteolytic "moonlighting" functions. Understanding these moonlighting proteases is crucial for developing effective antimicrobial therapies.

Keywords:
MicrobiologyMoonlightingMultifunctional proteinsPathogenesisProtease

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Area of Science:

  • Microbiology
  • Enzymology
  • Proteomics

Background:

  • Proteases are enzymes critical for protein hydrolysis, often acting as microbial virulence factors and targets for drug design.
  • Emerging evidence shows some proteases exhibit additional non-proteolytic "moonlighting" functions, impacting host interactions and complicating therapeutic strategies.
  • Moonlighting enzymes are multifunctional proteins with at least two distinct roles on a single polypeptide chain, often identified through empirical data and cell surface localization clues.

Purpose of the Study:

  • To highlight microbial proteases with significant non-proteolytic functions.
  • To explore the diverse "moonlighting" activities of these proteases and their contribution to microbial pathogenesis.
  • To discuss the implications of these dual functions for drug design and therapeutic interventions.

Main Methods:

  • Review and description of specific microbial proteases with identified non-proteolytic functions.
  • Analysis of how these moonlighting functions contribute to host cell adhesion, tissue invasion, and immune modulation.
  • Discussion of the role of proteomics in discovering moonlighting proteins within microbial exoproteomes.

Main Results:

  • Examples provided include streptococcal pyrogenic exotoxin B, PepO and C5a peptidases, mycoplasmal aminopeptidases, mycobacterial chaperones, and viral papain-like proteases.
  • Non-proteolytic functions identified include host cell adhesion, modulation of coagulation pathways, protein folding assistance, cell signaling participation, and expanded substrate repertoire.
  • Proteomics approaches have proven valuable in identifying potential moonlighting proteins in microbial exoproteomes.

Conclusions:

  • Microbial proteases can possess critical non-proteolytic "moonlighting" functions that influence virulence and host interactions.
  • These dual functions necessitate a comprehensive understanding for effective therapeutic target identification and drug design.
  • Further investigation into microbial exoproteomes using proteomics is essential for discovering novel moonlighting proteins.