NISCAIR Online Periodicals Repository

Research Journals >
Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.46 [2009] >
IJBB Vol.46(1) [February 2009] >

Title: Functionality of drug efflux pumps in antimonial resistant Leishmania donovani field isolates
Authors: Mandal, Goutam
Sarkar, Avijit
Saha, Piu
Singh, Neeloo
Sundar, Shyam
Chatterjee, Mitali
Keywords: Antimony resistance
Axenic amastigotes
Drug efflux pumps
Multidrug resistance protein (MRP)
Multidrug resistant (MDR)
Visceral leishmaniasis
Issue Date: Feb-2009
Publisher: CSIR
Abstract: The recent upsurge of antimony (Sb) resistance is a major impediment to successful chemotherapy of visceral leishmaniasis (VL). Mechanisms involved in antimony resistance have demonstrated an upregulation of drug efflux pumps; however, the biological role drug efflux pumps in clinical isolates remains to be substantiated. Thus, in this study, the functionality of drug efflux pumps was measured in promastigotes and axenic amastigotes isolated from VL patients, who were either Sb-sensitive (AG83, 2001 and MC9) or resistant (NS2, 41 and GE1) using rhodamine123 as a substrate for multidrug resistant (MDR) pumps and calcein as a substrate for multidrug resistance-associated proteins (MRP) respectively; their specificity was confirmed using established blockers. Sb-resistant (Sb-R) isolates accumulated higher amounts of R123, as compared to Sb-sensitive (Sb-S) isolates. Verapamil, a MDR inhibitor failed to alter R123 accumulation, suggesting absence of classical MDR activity. In Sb-R isolates, both promastigotes and axenic amastigotes accumulated significantly lower amounts of calcein than Sb-S isolates and probenecid, an established pan MRP blocker, marginally increased calcein accumulation. Depletion of ATP dramatically increased calcein accumulation primarily in Sb-R isolates, indicating existence of a MRP-like pump, which was more active in Sb-R isolates. In conclusion, our data suggested that overfunctioning of a MRP-like pump contributed towards generation of Sb-R phenotype in L. donovani field isolates.
Page(s): 86-92
ISSN: 0301-1208
Source:IJBB Vol.46(1) [February 2009]

Files in This Item:

File Description SizeFormat
IJBB 46(1) 86-92.pdf439.04 kBAdobe PDFView/Open
 Current Page Visits: 92 
Recommend this item


Online Submission of Articles |  NISCAIR Website |  National Knowledge Resources Consortium |  Contact us |  Feedback

Disclaimer: NISCAIR assumes no responsibility for the statements and opinions advanced by contributors. The editorial staff in its work of examining papers received for publication is helped, in an honorary capacity, by many distinguished engineers and scientists.

CC License Except where otherwise noted, the Articles on this site are licensed under Creative Commons License: CC Attribution-Noncommercial-No Derivative Works 2.5 India

Copyright © 2015 The Council of Scientific and Industrial Research, New Delhi. All rights reserved.

Powered by DSpace Copyright © 2002-2007 MIT and Hewlett-Packard | Compliant to OAI-PMH V 2.0

Home Page Total Visits: 168147 since 01-Sep-2015  Last updated on 29-Jun-2016Webmaster: