Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-09T22:52:04.176Z Has data issue: false hasContentIssue false
  • English
  • Français

Specific cpb copies within the Leishmania donovani complex: evolutionary interpretations and potential clinical implications in humans

Published online by Cambridge University Press:  28 November 2006

M. HIDE ,
R. BRAS-GONÇALVES  and
A. L. BAÑULS
M. HIDE
Affiliation:
Génétique et Evolution des Maladies Infectieuses, IRD/CNRS (UMR 2724), F-34394, France
R. BRAS-GONÇALVES
Affiliation:
IRD de Montpellier, Pathogénie des trypanosomatidés, UR08, 911, avenue Agropolis BP 64501, 34394 Montpellier Cedex 5, France
A. L. BAÑULS
Affiliation:
Génétique et Evolution des Maladies Infectieuses, IRD/CNRS (UMR 2724), F-34394, France
Get access Rights & Permissions [Opens in a new window]

Abstract

Leishmania infantum and Leishmania donovani both pertain to the L. (L.) donovani complex and are responsible for visceral leishmaniasis. To explore the L. donovani complex, we focused our study on cysteine protease B (cpb) and especially on 2 cpb copies: cpbE and cpbF. We selected cpb genes because of their phylogenetic interest and host–parasite interaction involvement. Sequencing these 2 copies revealed (i) that cpbE is specific to L. infantum and cpbF is specific to L. donovani and (ii) that these 2 copies are different in length and sequence.Nucleotide sequence data reported in this paper are available in the GenBank database under Accession numbers AY896776 AY896777, AY896778, AY896779, AY896780, AY896781, AY896782, AY896783, AY896784, AY896785, AY896786, AY896787, AY896788, AY896789, AY896790, AY896791. Phylogenetic analysis and protein predictions were carried out in order to compare these copies (i) with other trypanosomatid cpb, especially L. mexicana, and (ii) within the L. donovani complex. Our results revealed patterns specific to the L. donovani complex such as the COOH-terminal extension, potential epitopes and N-glycosylation sites. Moreover, phylogenetic analysis revealed different levels of polymorphism between L. infantum and L. donovani and confirmed the ancestral status of the latter. L. infantum has a shorter sequence and a deleted sequence responsible for modifications in protein conformation and catalytic triad. Considering the clinical aspect, L. infantum dermotropic strains appeared more polymorphic than L. infantum viscerotropic strains.

Keywords

cysteine protease BLeishmania donovani complexphylogenyprotein isoformsCOOH-terminal extension
Type
Research Article
Information
Parasitology , Volume 134 , Issue 3 , March 2007 , pp. 379 - 389
Copyright
© 2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alexander, J., Coombs, G. H. and Mottram, J. C. ( 1998). Leishmania mexicana cysteine proteinase-deficient mutants have attenuated virulence for mice and potentiate a Th1 response. Journal of Immunology 161, 6794–6801.Google Scholar
Beyrodt, C. G., Pinto, A. R., Freymuller, E. and Barbieri, C. L. ( 1997). Characterization of an antigen from Leishmania amazonensis amastigotes able to elicit protective responses in a murine model. Infection and Immunity 65, 2052–2059.Google Scholar
Boukai, L. K., Da Costa-Pinto, D., Soares, M. J., McMahon-Pratt, D. and Traub-Cseko, Y. M. ( 2000 a). Trafficking of cysteine proteinase to Leishmania lysosomes: lack of involvement of glycosylation. Molecular and Biochemical Parasitology 107, 321–325.Google Scholar
Boukai, L. K., McMahon-Pratt, D. and Traub-Cseko, Y. M. ( 2000 b). Evidence for a recent mutation giving rise to a truncated copy of a cysteine proteinase gene in Leishmania pifanoi. Parasitology International 49, 301–307.Google Scholar
Cazzulo, J. J., Martinez, J., Parodi, A. J., Wernstedt, C. and Hellman, U. ( 1992). On the post-translational modifications at the C-terminal domain of the major cysteine proteinase (cruzipain) from Trypanosoma cruzi. FEMS Microbiology Letters 79, 411–416.CrossRefGoogle Scholar
Chang, K. P. and McGwire, B. S. ( 2002). Molecular determinants and regulation of Leishmania virulence. Kinetoplastid Biology and Disease 1, 1.CrossRefGoogle Scholar
Chevenet, F., Brun, C., Bañuls, A. L., Jacq, B. and Christen, R. ( 2006). TreeDyn: towards dynamic graphics and annotations for analyses of trees. BMC Bioinformatics 7, 439.CrossRef
Coombs, G. H. and Mottram, J. C. ( 1997). Parasite proteinases and amino acid metabolism: possibilities for chemotherapeutic exploitation. Parasitology 114, S61–S80.Google Scholar
Dwek, R. A. ( 1998). Biological importance of glycosylation. Developments in Biological Standardization 96, 43–47.CrossRefGoogle Scholar
Felsenstein, J. ( 1981). Evolutionary trees from DNA sequences: a maximum likelihood approach. Journal of Molecular Evolution 17, 368–376.CrossRefGoogle Scholar
Frame, M. J., Mottram, J. C. and Coombs, G. H. ( 2000). Analysis of the roles of cysteine proteinases of Leishmania mexicana in the host-parasite interaction. Parasitology 121, 367–377.CrossRefGoogle Scholar
Ibrahim, M. E. ( 2002). The epidemiology of visceral leishmaniasis in east Africa: hints and molecular revelations. Transactions of the Royal Society of Tropical Medicine and Hygiene 96 (Suppl. 1), S25–S29.CrossRefGoogle Scholar
Ibrahim, M. E. and Barker, D. C. ( 2001). The origin and evolution of the Leishmania donovani complex as inferred from a mitochondrial cytochrome oxidase II gene sequence. Infection, Genetics and Evolution 1, 61–68.CrossRefGoogle Scholar
Judice, W. A., Mottram, J. C., Coombs, G. H., Juliano, M. A. and Juliano, L. ( 2005). Specific negative charges in cysteine protease isoforms of Leishmania mexicana are highly influential on the substrate binding and hydrolysis. Molecular and Biochemical Parasitology 144, 36–43.CrossRefGoogle Scholar
Jukes, T. H. and Cantor, C. R. ( 1969). Evolution of protein molecules. In Mammalian Protein Metabolism (ed. Munro, H. N.), pp. 21–132. Academic Press, New York.CrossRef
Juliano, M. A., Brooks, D. R., Selzer, P. M., Pandolfo, H. L., Judice, W. A., Juliano, L., Meldal, M., Sanderson, S. J., Mottram, J. C. and Coombs, G. H. ( 2004). Differences in substrate specificities between cysteine protease CPB isoforms of Leishmania mexicana are mediated by a few amino acid changes. European Journal of Biochemistry 271, 3704–3714.CrossRefGoogle Scholar
Kimura, M. ( 1980). A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. Journal of Molecular Evolution 16, 111–120.CrossRefGoogle Scholar
Mahmoudzadeh-Niknam, H. and McKerrow, J. H. ( 2004). Leishmania tropica: cysteine proteases are essential for growth and pathogenicity. Experimental Parasitology 106, 158–163.CrossRefGoogle Scholar
McGrath, M. E., Eakin, A. E., Engel, J. C., McKerrow, J. H., Craik, C. S. and Fletterick, R. J. ( 1995). The crystal structure of cruzain: a therapeutic target for Chagas' disease. Journal of Molecular Biology 247, 251–259.CrossRefGoogle Scholar
McKerrow, J. H., Engel, J. C. and Caffrey, C. R. ( 1999). Cysteine protease inhibitors as chemotherapy for parasitic infections. Bioorganic and Medicinal Chemistry 7, 639–644.CrossRefGoogle Scholar
Mottram, J. C., Brooks, D. R. and Coombs, G. H. ( 1998). Roles of cysteine proteinases of trypanosomes and Leishmania in host- parasite interactions. Current Opinion in Microbiology 1, 455–460.CrossRefGoogle Scholar
Mottram, J. C., Frame, M. J., Brooks, D. R., Tetley, L., Hutchison, J. E., Souza, A. E. and Coombs, G. H. ( 1997). The multiple cpb cysteine proteinase genes of Leishmania mexicana encode isoenzymes that differ in their stage regulation and substrate preferences. The Journal of Biological Chemistry 272, 14285–14293.CrossRefGoogle Scholar
Mottram, J. C., Souza, A. E., Hutchison, J. E., Carter, R., Frame, M. J. and Coombs, G. H. ( 1996). Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors. Proceedings of the National Academy of Sciences, USA 93, 6008–6013.CrossRefGoogle Scholar
Mundodi, V., Somanna, A., Farrell, P. J. and Gedamu, L. ( 2002). Genomic organization and functional expression of differentially regulated cysteine protease genes of Leishmania donovani complex. Gene 282, 257–265.CrossRefGoogle Scholar
Nakhaee, A., Taheri, T., Taghikhani, M., Mohebali, M., Salmanian, A. H., Fasel, N. and Rafati, S. ( 2004). Humoral and cellular immune responses against type I cysteine proteinase of Leishmania infantum are higher in asymptomatic than symptomatic dogs selected from a naturally infected population. Veterinary Parasitology 119, 107–123.CrossRefGoogle Scholar
Oskam, L., Pratlong, F., Zijlstra, E. E., Kroon, C. C., Dedet, I. P., Kager, P. A., Schonian, G., Ghalib, H. W., El-Hassan, A. M. and Meredith, S. E. ( 1998). Biochemical and molecular characterization of Leishmania parasites isolated from an endemic focus in eastern Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene 92, 120–122.CrossRefGoogle Scholar
Parodi, A. J., Labriola, C. and Cazzulo, J. J. ( 1995). The presence of complex-type oligosaccharides at the C-terminal domain glycosylation site of some molecules of cruzipain. Molecular and Biochemical Parasitology 69, 247–255.CrossRefGoogle Scholar
Pratlong, F., Dereure, J., Bucheton, B., El-Saf, S., Dessein, A., Lanotte, G. and Dedet, J. P. ( 2001). Sudan: the possible original focus of visceral leishmaniasis. Parasitology 122, 599–605.CrossRefGoogle Scholar
Quispe Tintaya, K. W., Ying, X., Dedet, J. P., Rijal, S., De Bolle, X. and Dujardin, J. C. ( 2004). Antigen genes for molecular epidemiology of leishmaniasis: polymorphism of cysteine proteinase B and surface metalloprotease glycoprotein 63 in the Leishmania donovani complex. Journal of Infectious Diseases 189, 1035–1043.CrossRefGoogle Scholar
Sacks, D. and Noben-Trauth, N. ( 2002). The immunology of susceptibility and resistance to Leishmania major in mice. Nature Reviews Immunology 2, 845–858.CrossRefGoogle Scholar
Sajid, M. and McKerrow, J. H. ( 2002). Cysteine proteases of parasitic organisms. Molecular and Biochemical Parasitology 120, 1–21.CrossRefGoogle Scholar
Selzer, P. M., Chen, X., Chan, V. J., Cheng, M., Kenyon, G. L., Kuntz, I. D., Sakanari, J. A., Cohen, F. E. and McKerrow, J. H. ( 1997). Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors. Experimental Parasitology 87, 212–221.CrossRefGoogle Scholar
Souza, A. E., Waugh, S., Coombs, G. H. and Mottram, J. C. ( 1992). Characterization of a multi-copy gene for a major stage-specific cysteine proteinase of Leishmania mexicana. FEBS Letters 311, 124–127.CrossRefGoogle Scholar
Thompson, J. D., Gibson, T. J., Plewniak, F., Jeanmougin, F. and Higgins, D. G. ( 1997). The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Research 25, 4876–4882.CrossRefGoogle Scholar
World Health Organization ( 2002). Annex 3: burden of disease in DALYs by cause, sex and mortality stratum in WHO regions, estimates for 2001, pp. 192–197. World Health Organization, Geneva.
Yang, Z. ( 1997). PAML: a program package for phylogenetic analysis by maximum likelihood. Computer Applications in the Biosciences 13, 555–556.CrossRefGoogle Scholar
Yang, Z. ( 2002). Inference of selection from multiple species alignments. Current Opinion in Genetics and Development 12, 688–694.CrossRefGoogle Scholar
Zemanova, E., Jirku, M., Mauricio, I. L., Miles, M. A. and Lukes, J. ( 2004). Genetic polymorphism within the Leishmania donovani complex: correlation with geographic origin. The American Society of Tropical Medicine and Hygiene 70, 613–617.Google Scholar