title: Leishmania tropica: cysteine proteases are essential for growth and pathogenicity.
abstract: Leishmania parasites are responsible for a diverse collection of diseases of humans and other animals. Cysteine proteases are putative virulence factors of leishmania parasites. There are differences in the susceptibility of specific stages in different Leishmania species to cysteine protease inhibitors. Here, we establish a key role of cysteine proteases in growth, viability, and pathogenicity of Leishmania tropica by using a specific cysteine protease inhibitor (N-Pip-F-hF-VS Phenyl). Reduction or arrest of promastigote growth occurred at inhibitor concentration of 5 and 100 microM, respectively. This shows an essential role for cysteine proteases in viability and growth of L. tropica promastigotes. It confirms that the promastigote stage of L. tropica more closely resembles that of Leishmania major than that of Leishmania mexicana, which is refractory to this inhibitor. Pathogenicity of L. tropica amastigotes in mice, as assessed by footpad swelling, was also reduced by treatment with the cysteine protease inhibitor. This suggests that cysteine proteases are essential for pathogenicity of L. tropica amastigote in mammalian host, similar to both L. major and L. mexicana.
authors.affiliation: Immunology Department, Pasteur Institute of Iran, Tehran 13164, Iran. mahmoudh@institute.pasteur.ac.ir
authors.forename: H
authors.initials: H
authors.lastname: Mahmoudzadeh-Niknam
authors.forename: J H
authors.initials: JH
authors.lastname: McKerrow
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D018320:Leishmania major / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity; D007895:Leishmania tropica / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology / Q000469:parasitology*; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives; D010879:Piperazines; D014105:Tosyl Compounds; D014753:Vinyl Compounds / Q000494:pharmacology*; D014774:Virulence / Q000502:physiology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D010879:Piperazines; D014105:Tosyl Compounds; D014753:Vinyl Compounds; C487484:N-pip-phenylalanine-homophenylalanine-vinyl sulfone phenyl; D010649:Phenylalanine; D003546:Cysteine Endopeptidases