Specific cpb copies within the Leishmania donovani complex: evolutionary interpretations and potential clinical implications in humans
Leishmania infantum and Leishmania donovani both pertain to the L. (L.) donovani complex and are responsible for visceral leishmaniasis. To explore the L. donovani complex, we focused our study on cysteine protease B (cpb) and especially on 2 cpb copies: cpbE and cpbF. We selected cpb genes because of their phylogenetic interest and host–parasite interaction involvement. Sequencing these 2 copies revealed (i) that cpbE is specific to L. infantum and cpbF is specific to L. donovani and (ii) that these 2 copies are different in length and sequence. 1 Phylogenetic analysis and protein predictions were carried out in order to compare these copies (i) with other trypanosomatid cpb, especially L. mexicana, and (ii) within the L. donovani complex. Our results revealed patterns specific to the L. donovani complex such as the COOH-terminal extension, potential epitopes and N-glycosylation sites. Moreover, phylogenetic analysis revealed different levels of polymorphism between L. infantum and L. donovani and confirmed the ancestral status of the latter. L. infantum has a shorter sequence and a deleted sequence responsible for modifications in protein conformation and catalytic triad. Considering the clinical aspect, L. infantum dermotropic strains appeared more polymorphic than L. infantum viscerotropic strains.(Received April 12 2006)
(Revised June 17 2006)
(Accepted August 22 2006)
(Published Online November 28 2006)
Key Words: cysteine protease B; Leishmania donovani complex; phylogeny; protein isoforms; COOH-terminal extension.
c1 Laboratory GEMI, UMR CNRS/IRD 2724, 911, avenue Agropolis BP 64501, 34394 Montpellier Cedex 5, France. Tel: +33 4 67 41 62 72. Fax: +33 4 67 41 62 99. E-mail: [email protected]
1 Nucleotide sequence data reported in this paper are available in the GenBank database under Accession numbers AY896776 AY896777, AY896778, AY896779, AY896780, AY896781, AY896782, AY896783, AY896784, AY896785, AY896786, AY896787, AY896788, AY896789, AY896790, AY896791.