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. 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.
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Génétique et Evolution des Maladies Infectieuses, IRD/CNRS (UMR 2724), F-34394, France. hide@mpl.ird.fr
Bras-Gonçalves
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D018628:Gene Dosage; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007893:Leishmania donovani / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D018314:Leishmania infantum / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000469:parasitology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA
D007527:Isoenzymes; D003546:Cysteine Endopeptidases