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Title: Conditional silencing of topoisomerase I gene of Mycobacterium tuberculosis validates its essentiality for cell survival
Authors: Ahmed, Wareed
Menon, Shruti
Godbole, Adwait Anand
Karthik, Pullela V. D. N. B.
Nagaraja, V.
Keywords: Microbiology
Mycobacterium Tuberculosis
Conditional Silencing
Essential Genes
Cell Growth
Topoisomerase I
Drug-Resistant Tuberculosis
DNA Topoisomerases
Issue Date: 2014
Publisher: Oxford University Press
Citation: Ahmed, W; Menon, S; Godbole, AA; Karthik, PVDNB; Nagaraja, V, Conditional silencing of topoisomerase I gene of Mycobacterium tuberculosis validates its essentiality for cell survival. Fems Microbiology Letters 2014, 353 (2) 116-123,
FEMS Microbiology Letters
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.
Description: Restricted Access
ISSN: 0378-1097
Appears in Collections:Research Articles (Nagaraja, V.)

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