Use of NMR metabolomics to analyze the targets of D-cycloserine in mycobacteria: role of D-alanine racemase

J Proteome Res. 2007 Dec;6(12):4608-14. doi: 10.1021/pr0704332. Epub 2007 Nov 3.

Abstract

D-Cycloserine (DCS) is only used with multidrug-resistant strains of tuberculosis because of serious side effects. DCS is known to inhibit cell wall biosynthesis, but the in vivo lethal target is still unknown. We have applied NMR-based metabolomics combined with principal component analysis to monitor the in vivo effect of DCS on Mycobacterium smegmatis. Our analysis suggests DCS functions by inhibiting multiple protein targets.

Publication types

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

MeSH terms

  • Alanine / physiology
  • Alanine Racemase / biosynthesis
  • Alanine Racemase / genetics
  • Alanine Racemase / metabolism
  • Alanine Racemase / physiology*
  • Antibiotics, Antitubercular / pharmacology*
  • Cycloserine / pharmacology*
  • Drug Resistance, Multiple, Bacterial
  • Magnetic Resonance Spectroscopy*
  • Mycobacterium smegmatis / drug effects
  • Mycobacterium smegmatis / enzymology*
  • Mycobacterium smegmatis / genetics
  • Mycobacterium smegmatis / growth & development
  • Peptidoglycan / biosynthesis
  • Proteome / metabolism*

Substances

  • Antibiotics, Antitubercular
  • Peptidoglycan
  • Proteome
  • Cycloserine
  • Alanine Racemase
  • Alanine