Parasitology Research

, Volume 112, Issue 9, pp 3305–3314 | Cite as

Activation of Leishmania spp. leishporin: evidence that dissociation of an inhibitor not only improves its lipid-binding efficiency but also endows it with the ability to form pores

  • Flávia Regina Almeida-Campos
  • Thiago Castro-Gomes
  • Alice Machado-Silva
  • Jamil Silvano de Oliveira
  • Marcelo Matos Santoro
  • Frédéric Frézard
  • Maria Fátima HortaEmail author
Original Paper


We have previously shown that various species of Leishmania produce a lytic activity, which, in Leishmania amazonensis, is mediated by a pore-forming cytolysin, called leishporin. It is toxic for macrophages in vitro and optimally active at pH 5.0 to 5.5 and at 37 °C, suggesting that it might be active inside phagolysosomes. Leishporin from both L. amazonensis (a-leishporin) and Leishmania guyanensis (g-leishporin) can be activated by proteases, suggesting either a limited proteolysis of an inactive precursor or a proteolytic degradation of a non-covalently linked inhibitor. Here, we show that both a- and g-leishporin are also activated in dissociating conditions, indicating the second hypothesis as the correct one. In fact, we further demonstrated that inactive leishporin is non-covalently associated with an inhibitor, possibly more than one oligopeptide that, when removed, renders leishporin hemolytically active. This activation was shown to be the result of both the improvement of leishporin’s ability to bind to phospholipids and the emergence of its pore-forming ability. In vitro results demonstrate that leishporin can be released by the parasites, as they evolve in axenic cultures, in an inactive form that can be activated. These results are compatible with our hypothesis that leishporin can be activated in the protease-rich, low pH, and dissociating environment of parasitophorous vacuoles, leading to disruption of both vacuoles and plasma membranes with the release of amastigotes.


DPPC Hemolytic Activity Inactive Form Limited Proteolysis Parasitophorous Vacuole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



3[(3-Cholamidopropyl) dimethyl-ammonio]-2-hydroxy-propanesulfonate


Dipalmitoylphosphatidyl choline




N-2-Hydroxyethylpiperazine-N’-2-ethanesulfonic acid


Inverse of the dilution that caused 50 % of hemolysis


Human erythrocytes


Promastigotes membrane detergent-soluble extract


Pore-forming protein(s)


Phosphate-buffered saline



We thank Elimar Faria’s technical assistance. Financial support: UNICEF/UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, and Programa de Apoio a Núcleos de Excelência. FRAC and TCG were supported by Coordenadoria de Aperfeiçoamento de Pessoal do Ensino Superior. MFH and FF are Conselho Nacional de Desenvolvimento Científico e Tecnológico research fellows.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Flávia Regina Almeida-Campos
    • 1
    • 3
  • Thiago Castro-Gomes
    • 1
    • 4
  • Alice Machado-Silva
    • 1
    • 5
  • Jamil Silvano de Oliveira
    • 1
  • Marcelo Matos Santoro
    • 1
  • Frédéric Frézard
    • 2
  • Maria Fátima Horta
    • 1
    Email author
  1. 1.Departamento de Bioquímica e Imunologia, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Departamento de Fisiologia e Biofísica, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Departamento de Ciências Fisiológicas, Instituto de Ciências BiológicasUniversidade Federal do AmazonasManausBrazil
  4. 4.Department of Cell Biology and Molecular GeneticsUniversity of MarylandCollege ParkUSA
  5. 5.Departamento de Química, Instituto de Ciências ExatasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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