title: Dehydroepiandosterone induction of increased resistance to vancomycin in Staphylococcus aureus clinical isolates (MSSA, MRSA).
abstract: OBJECTIVE
  To investigate whether dehydroepiandosterone (DHEA), an androgen present throughout life, alters the response of Staphylococcus aureus clinical isolates to vancomycin.
  
  
  RESULTS
  DHEA in physiologically relevant concentrations (0.1, 0.5, 1.0 and 5.0 micromol l(-1)) was tested for its effect on methicillin-sensitive S. aureus (MSSA, n = 53) and methicillin-resistant S. aureus (MRSA, n = 73) response to vancomycin using standard protocols. Mutant selection was determined by serial transfer of selected isolates (n = 5). DHEA-mediated at least a fourfold increase in vancomycin MIC for 42% of MSSA and 21% of MRSA. For five of the isolates (0.1 and 0.5 micromol l(-1) DHEA) the MIC was increased to levels (8 microg ml(-1)) defined as vancomycin-intermediate resistance.
  
  
  CONCLUSIONS
  Resistance was detected only in the presence of DHEA, and was not related to altered generation time, indicating induction of phenotypic resistance.
  
  
  CONCLUSIONS
  These findings require further investigation to determine what role DHEA plays in clinical vancomycin treatment failure that has been reported in the absence of vancomycin genotypic resistance or heteroresistance.
authors.affiliation: Department of Microbiology, Midwestern University, Downers Grove, IL 60515, USA. bplotk@midwestern.edu
authors.forename: B J
authors.initials: BJ
authors.lastname: Plotkin
authors.forename: A
authors.initials: A
authors.lastname: Morejon
authors.forename: R A
authors.initials: RA
authors.lastname: Laddaga
authors.forename: S M
authors.initials: SM
authors.lastname: Viselli
authors.forename: J
authors.initials: J
authors.lastname: Tjhio
authors.forename: P
authors.initials: P
authors.lastname: Schreckenberger
mesh_terms: D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D020536:Enzyme Activators / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D020536:Enzyme Activators; D003687:Dehydroepiandrosterone; D014640:Vancomycin