Leishmania major: disruption of signal peptidase type I and its consequences on survival, growth and infectivity.

Taheri Tahereh (1, 2) , Salmanian Ali-Hatef (2) , Elham Gholami (1) , Fatemeh Doustdari (1) , Farnaz Zahedifard (1) , Sima Rafati (1)

1 Institut Pasteur d'Iran
2 National Institute of Genetic Engineering and Biotechnology

Leishmania major (L. major) signal peptidase type I (SPase I) is an endopeptidase encoded by a single-copy gene. In all organisms, SPase I is responsible for removing the signal peptide from secretory pre-proteins and releasing mature proteins to cellular or extra-cellular space. In this study, the role of SPase I in L. major is investigated by gene deletion using homologous recombination (HR). The null mutant of SPase I was not possible to create, suggesting that SPase I is an essential gene for parasite survival. The obtained heterozygote mutant by disrupting one allele of SPase I in L. major showed significantly reduced level of infectivity in bone marrow-derived macrophages. In addition, the heterozygote mutants are unable to cause cutaneous lesion in susceptible BALB/c mice. This is the first report showing that SPase I may have an important role in Leishmania infectivity, e.g. in differentiation and survival of amastigotes. Apparently, the SPase I expression is not essential for in vitro growth of the parasite.

Mots clés: Signal peptidase type I; Leishmania major; Homologous recombination; Gene disruption

Domaines: Vaccinologie

Taheri Tahereh, Salmanian Ali-Hatef, Elham Gholami, Fatemeh Doustdari, Farnaz Zahedifard, et al.. Leishmania major: disruption of signal peptidase type I and its consequences on survival, growth and infectivity.. Experimental Parasitology, 2010, 126 (2), pp.135-45. ⟨10.1016/j.exppara.2010.04.009⟩. ⟨pasteur-00787030⟩