Genome-wide exploration of the drug action of capreomycin on Mycobacterium tuberculosis using Affymetrix oligonucleotide GeneChips.
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.
Fu
Li M
LM
Pacific Tuberculosis and Cancer Research Organization, 8 Corporate Park, Suite 300, Irvine, CA 92606, USA. lifu@patcar.org <lifu@patcar.org>
Shinnick
Thomas M
TM
D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D002207:Capreomycin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D008660:Metabolism / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012336:RNA, Ribosomal, 16S / Q000187:drug effects
D000904:Antibiotics, Antitubercular; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S; D002207:Capreomycin