Abstract
GP63 or leishmanolysin is the major surface protease of Leishmania spp. involved in parasite virulence and host cell interaction. As such, GP63 is a potential target of eventual vaccines against these protozoa. In the current study we evaluate the polymorphism of gp63 in Leishmania (Viannia) braziliensis isolated from two sets of American tegumentary leishmaniasis (ATL) cases from Corte de Pedra, Brazil, including 35 cases diagnosed between 1994 and 2001 and 6 cases diagnosed between 2008 and 2011. Parasites were obtained from lesions by needle aspiration and cultivation. Genomic DNA was extracted, and 405 bp fragments, including sequences encoding the putative macrophage interacting sites, were amplified from gp63 genes of all isolates. DNA amplicons were cloned into plasmid vectors and ten clones per L. (V.) braziliensis isolate were sequenced. Alignment of cloned sequences showed extensive polymorphism among gp63 genes within, and between parasite isolates. Overall, 45 different polymorphic alleles were detected in all samples, which could be segregated into two clusters. Cluster one included 25, and cluster two included 20 such genotypes. The predicted peptides showed overall conservation below 50%. In marked contrast, the conservation at segments with putative functional domains approached 90% (Fisher’s exact test p<0.0001). These findings show that gp63 is very polymorphic even among parasites from a same endemic focus, but the functional domains interacting with the mammalian host environment are conserved.
Highlights
The Leishmania species parasite cause a variety of clinical syndromes in individuals living in tropical and subtropical areas of the globe [1]
Forty-five alleles of gp63 could be distinguished among 410 clones of the gene fragment evaluated in thirty-five isolates of L. (V.) braziliensis collected between 1992 and 2001, and six isolates of the parasite drawn between 2008 and 2011 from American Tegumentary Leishmaniasis (ATL) patients of Corte de Pedra
Our prior work has underscored the fact that polymorphic isolates of L. (V.) braziliensis are independently associated with different clinical outcomes of infection [43, 44]
Summary
The Leishmania species parasite cause a variety of clinical syndromes in individuals living in tropical and subtropical areas of the globe [1]. More difficult to treat forms of ATL in the region include the classically recognized mucosal leishmaniasis (ML), and emerging clinical forms such as disseminated leishmaniasis (DL) and atypical cutaneous leishmaniasis (ACL). Patients with these unusual forms tend to respond poorly to Sb(V), with failure occurring in up to 60–90% of these individuals [10,11,12,13,14,15,16]. Such experience has led investigators to realize the need for new treatment modalities for ATL [9, 16, 17]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call