rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2002-11-27
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pubmed:abstractText |
We 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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-10200974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-10618433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-10639445,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-10655617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-11095745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-11254389,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-75545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-7615794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-7734942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-7849489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-7878014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-8757831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-9162010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-9212919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-9593053,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-9614254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-9634230,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12427974-9918109
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pubmed:language |
eng
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Alanine Racemase,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Bacterial,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate-Ammonia Ligase,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Bacterial,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/antigen 85A, Mycobacterium...,
http://linkedlifedata.com/resource/pubmed/chemical/antigen 85B, Mycobacterium...,
http://linkedlifedata.com/resource/pubmed/chemical/glutamine synthetase I
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pubmed:status |
MEDLINE
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pubmed:author |
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15614-9
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pubmed:dateRevised |
2009-11-18
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pubmed:articleTitle |
Targeting the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: Proof of principle by using antisense technology.
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pubmed:affiliation |
Division 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.
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