Linked Life Data

12427974

Source:http://linkedlifedata.com/resource/pubmed/id/12427974

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pubmed-article:12427974pubmed:abstractTextWe have investigated the effect of sequence-specific antisense phosphorothioate-modified oligodeoxyribonucleotides (PS-ODNs) targeting different regions of each of the 3032-kDa protein complex (antigen 85 complex) encoding genes on the multiplication of Mycobacterium tuberculosis. Single PS-ODNs to one of the three mycolyl transferase transcripts, added either once or weekly over the 6-wk observation period, inhibited bacterial growth by up to 1 log unit. A combination of three PS-ODNs specifically targeting all three transcripts inhibited bacterial growth by approximately 2 logs; the addition of these PS-ODNs weekly for 6 wk was somewhat more effective than a one-time addition. Targeting the 5' end of the transcripts was more inhibitory than targeting internal sites; the most effective PS-ODNs and target sites had minimal or no secondary structure. The effect of the PS-ODNs was specific, as mismatched PS-ODNs had little or no inhibitory activity. The antisense PS-ODNs, which were highly stable in M. tuberculosis cultures, specifically blocked protein expression by their gene target. PS-ODNs targeting the transcript of a related 24-kDa protein (mpt51) had little inhibitory effect by themselves and did not increase the effect of PS-ODNs against the three members of the 3032-kDa protein complex. The addition of PS-ODNs against the transcripts of glutamine synthetase I (glnA1) and alanine racemase (alr) modestly increased the inhibitory efficacy of the 3032-kDa protein complex-specific PS-ODNs to approximately 2.5 logs. This study shows that the three mycolyl transferases are highly promising targets for antituberculous therapy by using antisense or other antimicrobial technologies.lld:pubmed
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pubmed-article:12427974pubmed:authorpubmed-author:HorwitzMarcus...lld:pubmed
pubmed-article:12427974pubmed:authorpubmed-author:HarthGünterGlld:pubmed
pubmed-article:12427974pubmed:authorpubmed-author:TabatadzeDavi...lld:pubmed
pubmed-article:12427974pubmed:authorpubmed-author:ZamecnikPaul...lld:pubmed
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pubmed-article:12427974pubmed:dateRevised2009-11-18lld:pubmed
pubmed-article:12427974pubmed:articleTitleTargeting the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: Proof of principle by using antisense technology.lld:pubmed
pubmed-article:12427974pubmed:affiliationDivision of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles 90095, USA.lld:pubmed
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