Skip to main content
    • Aa
    • Aa

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

  • M. SAMANT (a1), A. A. SAHASRABUDDHE (a2), N. SINGH (a1), S. K. GUPTA (a1), S. SUNDAR (a3) and A. DUBE (a1)...

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.

Corresponding author
*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:,
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

S. L. Croft , S. Sundar and A. H. Fairlamb (2006). Drug resistance in leishmaniasis Clinical Microbiology Reviews 19, 111126.

A. Dube , N. Singh , S. Sundar and N. Singh (2005). Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persists in in vitro and in vivo experimental models. Parasitology Research 96, 216223.

B. Foth , A. Piani , J. M. Curtis , T. Ilg , M. McConville and E. Handman (2002). Leishmania major proteophosphoglycans exist as membrane-bound and soluble forms and localise to the cell membrane, the flagellar pocket and the lysosome. International Journal for Parasitology 32, 17011708.

U. Gopfert , N. Goehring , C. Klein and T. Ilg (1999). Proteophosphoglycans of Leishmania mexicana, Molecular cloning and characterization of the Leishmania mexicana PPG2 gene encoding the proteophosphoglycans aPPG and pPPG2 that are secreted by amastigotes and promastigotes. The Biochemical Journal 344, 787795.

P. J. Guerin , P. Olliaro , S. Sundar , M. Boelaert , S. L. Croft , P. Desjeux , M. K. Wasunna and A. D. M. Bryceson (2002). Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infectious Diseases 2, 494501.

T. Ilg (2000). Proteophosphoglycans of Leishmania. Parasitology Today 16, 489497.

T. Ilg , D. Craik , G. Currie , G. Multhaup and A. Bacic (1998). Stage-specific proteophosphoglycan from Leishmania mexicana amastigotes. Journal of Biological Chemistry 273, 1350913523.

T. Ilg , E. Handman , K. Ng , Y. D. Stierhof and A. Bacic (1999 b). Mucin-like proteophosphoglycans from the protozoan parasite Leishmania. Trends in Glycoscience and Glycotechnology 11, 119.

S. C. Ilgoutz and M. J. McConville (2001) Function and assembly of the Leishmania surface coat. International Journal for Parasitology 31, 899908.

L. Kedzierski , J. Montgomery , D. Bullen , J. Curtis , E. Gardiner , A. Jimenez-Ruiz and E. Handman (2004). A leucine-rich repeat motif of Leishmania parasite surface antigen 2 binds to macrophages through the complement receptor 3. Journal of Immunology 172, 49024906.

C. Klein , U. Gopfert , N. Goehring , Y. D. Stierhof and T. Ilg (1999). Proteophosphoglycans of Leishmania mexicana. Identification, purification, structural and ultra structural characterization of the secreted promastigote proteophosphoglycan pPPG2, a stage-specific glycoisoform of amastigote aPPG. The Biochemical Journal 344, 775786.

H. Kothari , P. Kumar , S. Sundar and N. Singh (2007). Possibility of membrane modification as a mechanism of antimony resistance in Leishmania. donovani. Parasitology International (in the Press) [Epub ahead of print] PMID: 17169604.

U. K. Laemmli (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227, 680685.

M. J. McConville and M. A. J. Ferguson (1993). The structure, biosynthesis and function of glycosylated-phosphatidylinositols in the parasitic protozoa and higher eukaryotes. The Biochemical Journal 294, 305324.

B. J. Mengeling , S. M. Beverley and S. J. Turco (1997). Designing glycoconjugate biosynthesis for an insidious intent: phosphoglycan assembly in Leishmania parasites. Glycobiology 7, 873880.

J. Montgomery , C. Curtis and E. Handman (2002). Genetic and structural heterogeneity of proteophosphoglycan in Leishmania. Molecular and Biochemical Parasitology 121, 7585.

J. Montgomery , T. Ilg , J. K. Thompson , B. Kobe and E. Handman (2000). Identification and predicted structure of a leucine-rich repeat motif shared by Leishmania major proteophosphoglycan and parasite surface antigen 2. Molecular and Biochemical Parasitology 107, 289295.

F. J. Perez-Victoria , S. Castanys and F. Gamarro (2003). Leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug. Antimicrobial Agents and Chemotherapy 47, 23972403.

A. Piani , T. Ilg , A. G. Elefanty , J. Curtis and E. Handman (1999). Leishmania major proteophosphoglycan is expressed by amastigotes and has an immunomodulatory effect on macrophage function. Microbes and Infection 1, 589599.

M. Rakotomanga , M. Saint-Pierre-Chazalet and P. M. Loiseau (2005). Alteration of fatty acid and sterol metabolism in miltefosine-resistant Leishmania donovani promastigotes and consequences for drug-membrane interactions. Antimicrobial Agents and Chemotherapy 49, 26772686.

M. E. Rogers , T. Ilg , A. V. Nikolaev , M. A. J. Ferguson and P. A. Bates (2004). Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature, London 430, 464467.

P. Sharma , N. Singh , R. Garg , W. Haq and A. Dube (2004). Efficacy of human β-casein fragment (54–59) and its synthetic analogue compound 89/215 against Leishmania donovani in hamsters. Peptides 25, 18731881.

A. K. Singh , B. Papadopoulou and M. Ouellette (2001). Gene amplification in amphotericin B-resistant Leishmania tarentolae. Experimental Parasitology 99, 141147.

N. Singh , R. Almeida , H. Kothari , P. Kumar , G. Mandal , M. Chatterjee , S. Venkatachalam , M. K. Govind , S. K. Mandal and S. Sundar (2007) Differential gene expression analysis in antimony unresponsive Indian kala azar (visceral leishmaniasis) clinical isolates by DNA microarray. Parasitology (in the Press) [Epub ahead of print] PMID: 17306059.

Y. D. Stierhof , P. A. Bates , R. L. Jacobson , M. E. Rogers , Y. Schlein , E Handman and T. Ilg (1999). Filamentous proteophosphoglycan secreted by Leishmania promastigotes forms gel-like three-dimensional networks that obstruct the digestive tract of infected sand fly vectors. European Journal of Cell Biology 78, 675689.

H. Towbin , T. Staehelin and J. Gordon (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences, USA 76, 43504354.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *