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Proteophosphoglycan is differentially expressed in sodium stibogluconate-sensitive and resistant Indian clinical isolates of Leishmania donovani

Published online by Cambridge University Press:  16 March 2007

M. SAMANT
Affiliation:
Divisions of ParasitologyCentral Drug Research Institute, Lucknow, India
A. A. SAHASRABUDDHE
Affiliation:
Molecular and Structural Biology, Central Drug Research Institute, Lucknow, India
N. SINGH
Affiliation:
Divisions of ParasitologyCentral Drug Research Institute, Lucknow, India
S. K. GUPTA
Affiliation:
Divisions of ParasitologyCentral Drug Research Institute, Lucknow, India
S. SUNDAR
Affiliation:
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
A. DUBE*
Affiliation:
Divisions of ParasitologyCentral Drug Research Institute, Lucknow, India
*
*Corresponding author: Division of Parasitology, Central Drug Research Institute, P.B. No. 173, Lucknow-226 001, India. Tel: +91 0522 2612411 18 Ext. 4398. Fax: +91 0522 2623938, 2623405. E-mail: [email protected], [email protected]

Summary

Leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (PPGs) some of which are secreted while others are found on the surface of promastigotes and amastigotes. These proteins are thought to be important in the transmission, invasion and subsequent intracellular survival of parasites. The structure and function of PPGs are species and stage-specific in the case of L. major and L. mexicana, but no such information has hitherto been available for L. donovani. This study presents, for the first time, an initial characterization (localization) of PPG in sodium stibogluconate (SSG)-resistant and sensitive clinical isolates of L. donovani from Bihar (India) by confocal microscopy, flow cytometry and Western blotting using antibodies to L. major PPG. Confocal microscopy analysis revealed that both promastigotes and amastigotes possess PPG on their cell membrane and flagellar pocket membrane but its expression was variable in different isolates. The quantitative analysis by FACS and Western blotting showed that the expression and intensity of PPG bands was higher in SSG-resistant isolates. This study suggests the possibilities of involvement of PPG in drug-resistant mechanisms and of using PPG abundance as a marker for identifying drug-resistant clinical isolates in Indian kala azar.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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