Parasitology

Research Article

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

M. SAMANTa1, A. A. SAHASRABUDDHEa2, N. SINGHa1, S. K. GUPTAa1, S. SUNDARa3 and A. DUBEa1 c1

a1 Divisions of Parasitology Central Drug Research Institute, Lucknow, India

a2 Molecular and Structural Biology, Central Drug Research Institute, Lucknow, India

a3 Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

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.

(Received December 01 2006)

(Revised January 09 2007)

(Accepted January 24 2007)

(Online publication March 16 2007)

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