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Evidence for the presence of R250G mutation at the ATPase domain of topoisomerase II in an arsenite-resistant Leishmania donovani exhibiting a differential drug inhibition profile.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Evidence for the presence of R250G mutation at the ATPase domain of topoisomerase II in an arsenite-resistant Leishmania donovani exhibiting a differential drug inhibition profile.
 
Creator Singh, Gaganmeet
Thakur, Meghna
Chakraborti, Pradip K
Dey, Chinmoy S
 
Subject QR Microbiology
 
Description Resistance to operational drugs is a major barrier to successful antileishmanial chemotherapy that demands development of novel drug intervention strategies based on rational approaches. Model drug resistance phenotypes, such as arsenite resistance used in the current study, facilitate our understanding of the mechanism of drug resistance and assist in identifying new drug target(s). The current study was undertaken to investigate the sensitivity of topoisomerase II (topo II) of arsenite-sensitive (Ld-Wt) and -resistant (Ld-As20) Leishmania donovani to antileishmanial/anti-topo II agents. The effect of antileishmanial/anti-topo II drugs on partially purified topo II enzyme from Ld-Wt and Ld-As20 revealed differential inhibition of topo II decatenation activity for the two strains, with a lower amount of drug required to inhibit activity by 50% in Ld-Wt compared with Ld-As20. Comparison of topo II sequences from both strains indicated a point mutation, R250G, in the ATPase domain of the resistant strain. Furthermore, the Arg-250 of the ATPase domain of topo II was observed to be conserved throughout different species of Leishmania. Variation in the topo II gene sequence between Ld-Wt and Ld-As20 is envisaged to be responsible for the differential behaviour of the enzymes from the two sources.
 
Publisher Elsevier Science
 
Date 2009-01
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1098/1/chakraborti2009.pdf
Singh, Gaganmeet and Thakur, Meghna and Chakraborti, Pradip K and Dey, Chinmoy S (2009) Evidence for the presence of R250G mutation at the ATPase domain of topoisomerase II in an arsenite-resistant Leishmania donovani exhibiting a differential drug inhibition profile. International journal of antimicrobial agents, 33 (1). pp. 80-5. ISSN 0924-8579
 
Relation http://www.sciencedirect.com/science/article/pii/S0924857908003336
http://crdd.osdd.net/open/1098/