Leishmania major: Disruption of signal peptidase type I and its consequences on survival, growth and infectivity |
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Authors: | Tahereh Taheri Ali-Hatef Salmanian Fatemeh Doustdari Sima Rafati |
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Affiliation: | a Molecular Immunology and Vaccine Research Lab, Pasteur Institute of Iran, Tehran, Iran b National Institute of Genetic Engineering and Biotechnology, Tehran, Iran |
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Abstract: | 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. |
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Keywords: | Signal peptidase type I Leishmania major Homologous recombination Gene disruption |
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