Making the cut: central roles of intramembrane proteolysis in pathogenic microorganisms

Nat Rev Microbiol. 2009 Jun;7(6):411-23. doi: 10.1038/nrmicro2130.


Proteolysis in cellular membranes to liberate effector domains from their transmembrane anchors is a well-studied regulatory mechanism in animal biology and disease. By contrast, the function of intramembrane proteases in unicellular organisms has received little attention. Recent progress has now established that intramembrane proteases execute pivotal roles in a range of pathogens, from regulating Mycobacterium tuberculosis envelope composition, cholera toxin production, bacterial adherence and conjugation, to malaria parasite invasion, fungal virulence, immune evasion by parasitic amoebae and hepatitis C virus assembly. These advances raise the exciting possibility that intramembrane proteases may serve as targets for combating a wide range of infectious diseases. This Review focuses on summarizing the advances, evaluating the limitations and highlighting the promise of this newly emerging field.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacteria / metabolism
  • Bacteria / pathogenicity
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Eukaryota / metabolism
  • Eukaryota / physiology
  • Fungi / metabolism
  • Fungi / physiology
  • Host-Pathogen Interactions
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Models, Biological
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / metabolism
  • Peptide Hydrolases / physiology*
  • Viruses / metabolism
  • Viruses / pathogenicity


  • Membrane Proteins
  • Peptide Hydrolases