Skip to main content

Advertisement

SpringerLink
Log in

Effect of A2 gene on infectivity of the nonpathogenic parasite Leishmania tarentolae

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Several species of protozoan parasites of the genus Leishmania are pathogenic to mammals and cause a wide spectrum of pathologies in human. However, the genus includes some species which infect reptiles. Leishmania tarentolae is a lizard pathogen absolutely nonpathogenic to mammals. Recent studies have shown that among some major virulence factors, A2 is absent in this species. First identified as an amastigote-specific gene in Leishmania donovani, A2 has been proved to play a major role in parasite virulence and visceralization capability. In this study, we have transfected A2 episomally into L. tarentolae and evaluated its effect on infectivity and survival of the parasites, in vitro and in vivo. During infection of in vitro-cultured intraperitoneal macrophages of BALB/c mice, A2-expressing L. tarentolae parasites demonstrated significantly higher level of infectivity in days 3 and 4 post-infection in comparison with the wild-type strain as control. Furthermore, in vivo infection showed that A2 has significantly increased the ability of L. tarentolae to survive in the liver of BALB/c mice. Altogether, our results show that A2 is functional in L. tarentolae, although through an unknown mechanism, and loss of A2 has been one of the factors partly contributing to the loss of virulence of L. tarentolae.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Azizi H, Hassani K, Taslimi Y, Shateri Najafabadi H, Papadopoulou B, Rafati S (2009) Searching for virulence factors in the non-pathogenic parasite to humans Leishmania tarentolae. Parasitology 136:723–735

    Article  PubMed  CAS  Google Scholar 

  • Badaro R, Jones TC, Carvalho EM (1986) New perspectives on a subclinical form of visceral leishmaniasis. J Infect Dis 154:1003–1011

    Article  PubMed  CAS  Google Scholar 

  • Bogdan C, Röllinghoff M (1999) How do protozoan parasites survive inside macrophages? Parasitol Today 15:22–28

    Article  PubMed  CAS  Google Scholar 

  • Breton M, Tremblay MJ, Ouellette M, Papadopoulou B (2005) Live nonpathogenic parasitic vector as a candidate vaccine against visceral leishmaniasis. Infect Immun 73:6372–6382

    Article  PubMed  CAS  Google Scholar 

  • Briones MRS, Nelson K, Beverley SM, Affonso HT, Camargo EP, Floeter-Winter LM (1992) Leishmania tarentolae taxonomic relatedness inferred from phylogenetic analysis of the small subunit ribosomal RNA gene. Mol Biochem Parasitol 53:121–128

    Article  PubMed  CAS  Google Scholar 

  • Chang KP, Chaudhuri G, Fong D (1990) Molecular determinants of Leishmania virulence. Annu Rev Microbiol 44:499–529

    Article  PubMed  CAS  Google Scholar 

  • Chang KP, Akman L, Nielsen JS (1999) Leishmania virulence and genetic heterogeneity. Clin Dermatol 17:269–273

    Article  PubMed  CAS  Google Scholar 

  • Chang K, Reed SG, McGwire BS, Soong L (2003) Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity. Acta Trop 85:375–380

    Article  PubMed  Google Scholar 

  • Charest H, Matlashewski G (1994) Developmental gene expression in Leishmania donovani: differential cloning and analysis of an amastigote stage-specific gene. Mol Cell Biol 14:2975–2984

    PubMed  CAS  Google Scholar 

  • Croan DG, Morrison DA, Ellis JT (1997) Evolution of the genus Leishmania revealed by comparison of DNA and RNA polymerase gene sequences. Mol Biochem Parasitol 89:149–159

    Article  PubMed  CAS  Google Scholar 

  • Desjeux P (2004) Leishmaniasis. Nat Rev Microbiol 2:692–693

    Article  PubMed  Google Scholar 

  • Fu G, Kolesnikov AA (1994) Leishmania gymnodactyli and Leishmania infantum minicircles contain the same guide RNA genes as do minicircles of Leishmania tarentolae. Mol Biochem Parasitol 67:171–174

    Article  PubMed  CAS  Google Scholar 

  • Garin YJ, Meneceur P, Pratlong F, Dedet JP, Derouin F, Lorenzo F (2005) A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene. BMC Infect Dis 5:18. doi:10.1186/1471-2334-5-18

    Article  PubMed  Google Scholar 

  • Ghedin E, Zhang WW, Charest H, Sundar S, Kenney RT, Matlashewski G (1997) Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis. Clin Diagn Lab Immunol 4:530–535

    PubMed  CAS  Google Scholar 

  • Gomez-Eichelmann MC, Holz G Jr, Beach D, Simpson AM, Simpson L (1988) Comparison of several lizard Leishmania species and strains in terms of kinetoplast minicircle and maxicircle DNA sequences, nuclear chromosomes, and membrane lipids. Mol Biochem Parasitol 27:143–158

    Article  PubMed  CAS  Google Scholar 

  • Lainson R, Shaw JJ (1987) Evolution, classification and geographical distribution of Leishmania. In: Peters W, Killick-Kendrick R (eds) The leishmaniasis in biology and medicine. Academic, London, pp 1–120

    Google Scholar 

  • Luyo-Acero GE, Uezato H, Oshiro M, Takei K, Kariya K, Katakura K, Gomez EAL, Hashiguchi Y, Nonaka S (2004) Sequence variation of the cytochrome b gene of various human infecting members of the genus Leishmania and their phylogeny. Parasitology 128:483–491

    Article  PubMed  CAS  Google Scholar 

  • McCall L, Matlashewski G (2010) Localization and induction of the A2 virulence factor in Leishmania: evidence that A2 is a stress response protein. Mol Microbiol 77:518–530

    Article  PubMed  CAS  Google Scholar 

  • Mizbani A, Taheri T, Zahedifard F, Taslimi Y, Azizi H, Azadmanesh K, Papadopoulou B, Rafati S (2010) Recombinant Leishmania tarentolae expressing the A2 virulence gene as a novel candidate vaccine against visceral leishmaniasis. Vaccine 28:53–62

    Article  CAS  Google Scholar 

  • Molyneux DH, Ashford RW (1983) The biology of Trypanosoma and Leishmania, parasites of man and domestic animals. Taylor & Francis, London

    Google Scholar 

  • Pearson RD, De Queiroz Sousa A (1996) Clinical spectrum of leishmaniasis. Clin Infect Dis 22:1–13

    Article  PubMed  CAS  Google Scholar 

  • Prina E, Roux E, Mattei D, Milon G (2007) Leishmania DNA is rapidly degraded following parasite death: an analysis by microscopy and real-time PCR. Microbes Infect 9:1307–1315

    Article  PubMed  CAS  Google Scholar 

  • Probst P, Stromberg E, Ghalib HW, Mozel M, Badaro R, Reed SG, Webb JR (2001) Identification and characterization of T cell-stimulating antigens from Leishmania by CD4 T cell expression cloning. J Immunol 166:498–505

    PubMed  CAS  Google Scholar 

  • Rafati S, Zahedifard F, Nazgouee F (2006) Prime-boost vaccination using cysteine proteinases type I and II of Leishmania infantum confers protective immunity in murine visceral leishmaniasis. Vaccine 24:2169–2175

    Article  PubMed  CAS  Google Scholar 

  • Remme JH, Blas E, Chitsulo L, Desjeux PM, Engers HD, Kanyok TP, Kengeya Kayondo JF, Kioy DW, Kumaraswami V, Lazdins JK, Nunn PP, Oduola A, Ridley RG, Toure YT, Zicker F, Morel CM (2002) Strategic emphases for tropical diseases research: a TDR perspective. Trends Parasitol 18:421–426

    Article  PubMed  Google Scholar 

  • Requena JM, Alonso C, Soto M (2000) Evolutionarily conserved proteins as prominent immunogens during Leishmania infections. Parasitol Today 16:246–250

    Article  PubMed  CAS  Google Scholar 

  • Rittig MG, Bogdan C (2000) Leishmania-host-cell interaction: complexities and alternative views. Parasitol Today 16:292–297

    Article  PubMed  CAS  Google Scholar 

  • Sereno DE, Cordeiro da Silva A, Mathieu-Daude F, Ouaissi A (2007) Advances and perspectives in Leishmania cell based drug-screening procedures. Parasitol Int 56:3–7

    Article  PubMed  CAS  Google Scholar 

  • Shaw JJ (1994) Taxonomy of the genus Leishmania: present and future trends and their implications. Mem Inst Oswaldo Cruz 89:471–478

    Article  PubMed  CAS  Google Scholar 

  • Silvestre R, Cordeiro-Da-Silva A, Santarém N, Vergnes B, Sereno D, Ouaissi A (2007) SIR2-deficient Leishmania infantum induces a defined IFN-γ/IL-10 pattern that correlates with protection. J Immunol 179:3161–3170

    PubMed  CAS  Google Scholar 

  • Wallbanks K, Maazoun R, Canning EU, Rioux JA (1985) The identity of Leishmania tarentolae Wenyon 1921. Parasitology 90:67–78

    Article  PubMed  Google Scholar 

  • Wenyon DM (1921) Observations on the intestinal protozoa of three Egyptian lizards, with a note on a cell-invading fungus. Parasitology 12:133–140

    Google Scholar 

  • World Health Organization (1990a) Control of the Leishmaniasis. WHO Expert Committee Technical Report Series No. 793. World Health Organization, Geneva

    Google Scholar 

  • World Health Organization (1990b) The Leishmaniasis. WHO Expert Committee Technical Report Series No. 793. World Health Organization, Geneva

    Google Scholar 

  • Zhang WW, Matlashewski G (1997) Loss of virulence in Leishmania donovani deficient in an amastigote-specific protein, A2. Proc Natl Acad Sci USA 94:8807–8811

    Article  PubMed  CAS  Google Scholar 

  • Zhang WW, Matlashewski G (2001) Characterization of the A2-A2rel gene cluster in Leishmania donovani: involvement of A2 in visceralization during infection. Mol Microbiol 39:935–948

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Charest H, Ghedin E, Matlashewski G (1996) Identification and overexpression of the A2 amastigote-specific protein in Leishmania donovani. Mol Biochem Parasitol 78:79–90

    Article  PubMed  CAS  Google Scholar 

  • Zhang WW, Mendez S, Ghosh A, Myler P, Ivens A, Clos J, Sacks DL, Matlashewski G (2003) Comparison of the A2 gene locus in Leishmania donovani and Leishmania major and its control over cutaneous infection. J Biol Chem 278:35508–35515

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran

    Amir Mizbani, Yasaman Taslimi, Farnaz Zahedifard, Tahereh Taheri & Sima Rafati

  2. Department of Biotechnology, University College of Science, University of Tehran, Tehran, Iran

    Amir Mizbani

Authors
  1. Amir Mizbani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasaman Taslimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Farnaz Zahedifard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tahereh Taheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sima Rafati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sima Rafati.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mizbani, A., Taslimi, Y., Zahedifard, F. et al. Effect of A2 gene on infectivity of the nonpathogenic parasite Leishmania tarentolae . Parasitol Res 109, 793–799 (2011). https://doi.org/10.1007/s00436-011-2325-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-011-2325-4

Keywords

Search

Navigation