Genome-wide exploration of the drug action of capreomycin on Mycobacterium tuberculosis using Affymetrix oligonucleotide GeneChips.

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Fu LM, Shinnick TM

Genome-wide exploration of the drug action of capreomycin on Mycobacterium tuberculosis using Affymetrix oligonucleotide GeneChips.

J Infect. 2007 Mar;54(3):277-84. doi: 10.1016/j.jinf.2006.05.012. Epub 2006 Jul 5.

PubMed ID

16822547 [ View in PubMed

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Abstract

OBJECTIVE: Multi-drug resistance and latent infection are two major issues in current tuberculosis (TB) control and management. Capreomycin is an important drug used for TB with multi-drug resistance. A recent study also indicates that this drug possesses unique bactericidal activity against non-replicating TB bacilli among known anti-TB drugs. Thus, there is an urgent need for investigating the full-spectrum action of capreomycin. METHODS: Here we conduct the first microarray-based study on capreomycin using the high-resolution Affymetrix oligonucleotide GeneChip system. RESULTS: The results indicate that capreomycin primarily acts on the information pathways but it also significantly affects cell wall, cell processes, intermediate metabolism and respiration in Mycobacterium tuberculosis. CONCLUSIONS: This study not only transcriptionally validates the specific molecular target, 16S rRNA, but also discovers potential new targets of capreomycin, including genes operating at the DNA level, such as Rv0054 (ssb) and Rv3715c (recR), as well as genes involved in cell division like Rv3260c (whiB2). In addition, the nuo gene cluster and the ATP synthase gene cluster are repressed.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Capreomycin	16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA	Protein	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Yes	Inhibitor	Details