Conditional silencing of topoisomerase I gene of Mycobacterium tuberculosis validates its essentiality for cell survival. Issue 2 (3rd April 2014)

• Record Type: Journal Article
• Authors: Ahmed, Wareed; Menon, Shruti; Godbole, Adwait Anand; Karthik, Pullela V.D.N.B.; Nagaraja, Valakunja
• Is Part Of: FEMS microbiology letters. Volume 353:Issue 2(2014:Apr.)
• Page Start: 116
• Page End: 123
• Publication Date: 2014-04-03
• Subjects: Microbiology -- Periodicals; 579
• DOI: 10.1111/1574-6968.12412
• Languages: English
• ISSNs: 0378-1097

Abstract

<abstract abstract-type="main" id="fml12412-abs-0001"> <title>Abstract</title> <p>Topoisomerases are an important class of enzymes for regulating the DNA transaction processes. <italic>Mycobacterium tuberculosis (Mtb)</italic> 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 <italic>M. tuberculosis</italic> topoisomerase I (TopoI^Mt) for bacterial growth and survival, we have generated a conditionally regulated strain of <italic>topoI</italic> in <italic>Mtb</italic>. 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 <italic>M. tuberculosis</italic> growth and open up new avenues for targeting the enzyme.</p> </abstract>