Activated ADI pathway: the initiator of intermediate vancomycin resistance in Staphylococcus aureus

Can J Microbiol. 2017 Mar;63(3):260-264. doi: 10.1139/cjm-2016-0439. Epub 2016 Oct 19.

Abstract

Comparative proteomic profiling between 2 vancomycin-intermediate Staphylococcus aureus (VISA) strains, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm, and vancomycin-susceptible S. aureus (VSSA) strain Mu50Ω revealed upregulated levels of catabolic ornithine carbamoyltransferase (ArcB) of the arginine catabolism pathway in VISA strains. Subsequent analyses showed that the VISA strains have higher levels of cellular ATP and ammonia, which are by-products of arginine catabolism, and displayed thicker cell walls. We postulate that elevated cytoplasmic ammonia and ATP molecules, resulting from activated arginine catabolism upon acquisition of vraS and graR mutations, are important requirements facilitating cell wall biosynthesis, thereby contributing to thickened cell wall and consequently reduced vancomycin susceptibility in VISA strains.

Keywords: ATP; Staphylococcus aureus de résistance intermédiaire à la vancomycine; ammonia; ammoniac; arginine catabolism; catabolisme de l’arginine; cell wall thickening; vancomycin-intermediate Staphylococcus aureus; épaississement de la paroi cellulaire.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Arginine / metabolism
  • Bacterial Proteins / genetics
  • Enzyme Activation
  • Gene Expression Profiling
  • Humans
  • Hydrolases / metabolism*
  • Microbial Sensitivity Tests
  • Mutation
  • Proteome
  • Staphylococcal Infections
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / genetics
  • Vancomycin / pharmacology*
  • Vancomycin Resistance* / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Proteome
  • Vancomycin
  • Arginine
  • Hydrolases
  • arginine deiminase