Use of NMR Metabolomics To Analyze the Targets of d-Cycloserine in Mycobacteria: Role of d-Alanine Racemase

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 moni...

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Bibliographic Details
Published inJournal of proteome research Vol. 6; no. 12; pp. 4608 - 4614
Main Authors Halouska, Steven, Chacon, Ofelia, Fenton, Robert J, Zinniel, Denise K, Barletta, Raul G, Powers, Robert
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 01.12.2007
Subjects
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
Metabolomics
NMR
Tuberculosis
Mycobacterium smegmatis
d-alanine racemase
d-cycloserine
Principal Component Analysis
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Summary: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.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr0704332