The Staphylococcus aureus leucine aminopeptidase is localized to the bacterial cytosol and demonstrates a broad substrate range that extends beyond leucine

Biol Chem. 2013 Jun;394(6):791-803. doi: 10.1515/hsz-2012-0308.

Abstract

Staphylococcus aureus is a potent pathogen of humans exhibiting a broad disease range, in part due to an extensive repertoire of secreted virulence factors, including proteases. Recently, we identified the first example of an intracellular protease (leucine aminopeptidase, LAP) that is required for virulence in S. aureus. Disruption of pepZ, the gene encoding LAP, had no affect on the growth rate of bacteria; however, in systemic and localized infection models the pepZ mutant had significantly attenuated virulence. Recently, a contradictory report was published suggesting that LAP is an extracellular enzyme and it is required for growth in S. aureus. Here, we investigate these results and confirm our previous findings that LAP is localized to the bacterial cytosol and is not required for growth. In addition, we conduct a biochemical investigation of purified recombinant LAP, identifying optimal conditions for enzymatic activity and substrate preference for hydrolysis. Our results show that LAP has a broad substrate range, including activity against the dipeptide cysteine-glycine, and that leucine is not the primary target of LAP.

Publication types

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

MeSH terms

  • Bacterial Proteins / metabolism*
  • Biofilms / drug effects
  • Blotting, Western
  • Cytosol / drug effects
  • Cytosol / enzymology*
  • Hydrogen-Ion Concentration / drug effects
  • Hydrolysis / drug effects
  • Intracellular Space / enzymology
  • Leucine / analogs & derivatives
  • Leucine / metabolism*
  • Leucine / pharmacology
  • Leucyl Aminopeptidase / antagonists & inhibitors
  • Leucyl Aminopeptidase / metabolism*
  • Metals / pharmacology
  • Recombinant Proteins / metabolism
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / enzymology*
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / physiology
  • Substrate Specificity / drug effects

Substances

  • Bacterial Proteins
  • Metals
  • Recombinant Proteins
  • Leucyl Aminopeptidase
  • Leucine
  • ubenimex