Metabolic mitigation of staphylococcus aureus vancomycin intermediate-level susceptibility

Stewart G. Gardner, Darrell D. Marshall, Robert S. Daum, Robert Powers, Greg A. Somerville

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Staphylococcus aureus is a major human pathogen whose infections are increasingly difficult to treat due to increased antibiotic resistance, including resistance to vancomycin. Vancomycin-intermediate S. aureus (VISA) strains develop resistance to vancomycin through adaptive changes that are incompletely understood. Central to this adaptation are metabolic changes that permit growth in the presence of vancomycin. To define the metabolic changes associated with adaptive resistance to vancomycin in S. aureus, the metabolomes of a vancomycin-sensitive and VISA strain pair isolated from the same patient shortly after vancomycin therapy began and following vancomycin treatment failure were analyzed. The metabolic adaptations included increases in acetogenesis, carbon flow through the pentose phosphate pathway, wall teichoic acid and peptidoglycan precursor biosynthesis, purine biosynthesis, and decreased tricarboxylic acid (TCA) cycle activity. The significance of these metabolic pathways for vancomycin-intermediate susceptibility was determined by assessing the synergistic potential of human-use-approved inhibitors of these pathways in combination with vancomycin against VISA strains. Importantly, inhibitors of amino sugar and purine biosynthesis acted synergistically with vancomycin to kill a diverse set of VISA strains, suggesting that combinatorial therapy could augment the efficacy of vancomycin even in patients infected with VISA strains.

Original languageEnglish (US)
Article numbere01608
JournalAntimicrobial Agents and Chemotherapy
Issue number1
StatePublished - Jan 2018


  • Metabolism
  • Physiology
  • Staphylococcus aureus
  • Vancomycin resistance

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


Dive into the research topics of 'Metabolic mitigation of staphylococcus aureus vancomycin intermediate-level susceptibility'. Together they form a unique fingerprint.

Cite this