Conditional silencing of topoisomerase I gene of Mycobacterium tuberculosis validates its essentiality for cell survival

Ahmed, Wareed and Menon, Shruti and Godbole, Adwait Anand and Karthik, Pullela VDNB and Nagaraja, Valakunja (2014) Conditional silencing of topoisomerase I gene of Mycobacterium tuberculosis validates its essentiality for cell survival. In: FEMS MICROBIOLOGY LETTERS, 353 (2). pp. 116-123.

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Abstract

Topoisomerases are an important class of enzymes for regulating the DNA transaction processes. Mycobacterium tuberculosis (Mtb) is one of the most formidable pathogens also posing serious challenges for therapeutic interventions. The organism contains only one type IA topoisomerase (Rv3646c), offering an opportunity to test its potential as a candidate drug target. To validate the essentiality of M.tuberculosis topoisomerase I (TopoI(Mt)) for bacterial growth and survival, we have generated a conditionally regulated strain of topoI in Mtb. The conditional knockdown mutant exhibited delayed growth on agar plate. In liquid culture, the growth was drastically impaired when TopoI expression was suppressed. Additionally, novobiocin and isoniazid showed enhanced inhibitory potential against the conditional mutant. Analysis of the nucleoid revealed its altered architecture upon TopoI depletion. These studies establish the essentiality of TopoI for the M.tuberculosis growth and open up new avenues for targeting the enzyme.

Item Type:	Journal Article
Publication:	FEMS MICROBIOLOGY LETTERS
Publisher:	WILEY-BLACKWELL
Additional Information:	Copyright for this article belongs to the WILEY-BLACKWELL, USA
Keywords:	Mycobacterium tuberculosis; conditional silencing; essential genes; cell growth; topoisomerase I
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	03 Jun 2014 08:29
Last Modified:	03 Jun 2014 08:30
URI:	http://eprints.iisc.ac.in/id/eprint/49098

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