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Inositol-1-phosphate synthetase mRNA as a new target for antisense inhibition of Mycobacterium tuberculosis

Paper ID Volume ID Publish Year Pages File Format Full-Text
25314 43567 2007 9 PDF Available
Title
Inositol-1-phosphate synthetase mRNA as a new target for antisense inhibition of Mycobacterium tuberculosis
Abstract

The need for novel antimicrobial agents to combat the emergence of multi-drug-resistant strains of Mycobacterium tuberculosis is a worldwide urgency. This study has investigated the effects on phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of inositol-1-phosphate synthase, the key enzyme in the first step in inositol synthesis. Inositol is utilized by M. tuberculosis in the production of its major thiol, which is an antioxidant that helps M. tuberculosis to get rid of reactive oxygen species and electrophilic toxins. Real-time RT-PCR analysis revealed that mRNA expression of inositol-1-phosphate (I-1-P) synthase was significantly reduced upon addition of 20 μM PS-ODNs. Treatment with antisense PS-ODNs also reduced the level of mycothiol and the proliferation of M. tuberculosis and enhanced susceptibility to antibiotics. The experiments indicated that the antisense PS-ODNs could enter the cytoplasm of M. tuberculosis and inhibit the expression of I-1-P synthase. This study demonstrates that the M. tuberculosis I-1-P synthase is a target for the development of novel antibiotics and PS-ODN to I-1-P synthase is a promising antimycobaterial candidate.

Keywords
mBBr, monobromobimane; ODN, oligonucleotides; PS-ODNs, phosphorothioate-modified oligonucleotides; HPLC, high performance liquid chromatography; TB, tuberculosis; ino1, inositol-1-phosphate synthetase; HIV, human immunodeficiency virus; RT-PCR, real-time
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Inositol-1-phosphate synthetase mRNA as a new target for antisense inhibition of Mycobacterium tuberculosis
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 128, Issue 4, 10 March 2007, Pages 726–734
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us