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 monitor the in vivo effect of DCS on Mycobacterium smegmatis. Our analysis suggests DCS functions by inhibiting multiple protein targets.
Halouska
Steven
S
Department of Chemistry, University of Nebraska Lincoln, Lincoln, Nebraska 68522, USA.
Chacon
Ofelia
O
Fenton
Robert J
RJ
Zinniel
Denise K
DK
Barletta
Raul G
RG
Powers
Robert
R
D000409:Alanine / Q000502:physiology; D000411:Alanine Racemase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D009682:Magnetic Resonance Spectroscopy; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D010457:Peptidoglycan / Q000096:biosynthesis; D020543:Proteome / Q000378:metabolism*
D000904:Antibiotics, Antitubercular; D010457:Peptidoglycan; D020543:Proteome; D003523:Cycloserine; D000411:Alanine Racemase; D000409:Alanine