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Repertoire, genealogy and genomic organization of cruzipain and homologous genes in Trypanosoma cruzi, T. cruzi-like and other trypanosome species.

Lima L, Ortiz PA, da Silva FM, Alves JM, Serrano MG, Cortez AP, Alfieri SC, Buck GA, Teixeira MM - PLoS ONE (2012)

Bottom Line: In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species.Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs.Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, ICB, Universidade de São Paulo, São Paulo, São Paulo, Brasil.

ABSTRACT
Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

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Network and polymorphism analyses on catalytic domain of cruzipain genes from different trypanosome species.Genes from Schizotrypanum species (T. cruzi, T. c. marinkellei and T. dionisii) were compared with homologues from their closest relative species, T. rangeli, and the distant related T. b. brucei. (A) Network of 33 amino acid predicted sequences constructed using the Neighbour-Net algorithm excluding all conserved sites and with Uncorrected p-distance. The numbers in nodes correspond to bootstrap values from 100 replicates. (B) Polymorphism on cruzipain amino acid sequences from the distinct trypanosome species.
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pone-0038385-g003: Network and polymorphism analyses on catalytic domain of cruzipain genes from different trypanosome species.Genes from Schizotrypanum species (T. cruzi, T. c. marinkellei and T. dionisii) were compared with homologues from their closest relative species, T. rangeli, and the distant related T. b. brucei. (A) Network of 33 amino acid predicted sequences constructed using the Neighbour-Net algorithm excluding all conserved sites and with Uncorrected p-distance. The numbers in nodes correspond to bootstrap values from 100 replicates. (B) Polymorphism on cruzipain amino acid sequences from the distinct trypanosome species.

Mentions: To study the relationships of cruzipain genes from all T. cruzi DTUs, T. c. marinkellei and T. dionisii, and homologues from T. rangeli and T. b. brucei (Table 1), we aligned ∼500 bp cdCATL sequences obtained in this study with the corresponding genes from T. cruzi CL Brener (Esmeraldo-like and non-Esmeraldo-like haplotypes), Esmeraldo cl3, JR cl4, M6241 cl6 and Sylvio X10.6. The analyses of either amino acid (Fig. 3) or nucleotide sequences (data not shown) generated networks of cruzipain genes with similar topologies. Sequences of cd-cruzipain from all T. cruzi DTUs always clustered together in a homogeneous assemblage (∼1.2% amino acid sequence divergence) separated from T. c marinkellei (5.5% divergence), and largely divergent from the cluster formed by T. dionisii from Brazil (20%) and Europe (21%). Amino acid sequences of cruzipain genes of all Schizotrypanum species clustered together and largely separated (28%) from the homologous genes of T. rangeli and T. b. brucei (Fig. 3; Table 1).


Repertoire, genealogy and genomic organization of cruzipain and homologous genes in Trypanosoma cruzi, T. cruzi-like and other trypanosome species.

Lima L, Ortiz PA, da Silva FM, Alves JM, Serrano MG, Cortez AP, Alfieri SC, Buck GA, Teixeira MM - PLoS ONE (2012)

Network and polymorphism analyses on catalytic domain of cruzipain genes from different trypanosome species.Genes from Schizotrypanum species (T. cruzi, T. c. marinkellei and T. dionisii) were compared with homologues from their closest relative species, T. rangeli, and the distant related T. b. brucei. (A) Network of 33 amino acid predicted sequences constructed using the Neighbour-Net algorithm excluding all conserved sites and with Uncorrected p-distance. The numbers in nodes correspond to bootstrap values from 100 replicates. (B) Polymorphism on cruzipain amino acid sequences from the distinct trypanosome species.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369871&req=5

pone-0038385-g003: Network and polymorphism analyses on catalytic domain of cruzipain genes from different trypanosome species.Genes from Schizotrypanum species (T. cruzi, T. c. marinkellei and T. dionisii) were compared with homologues from their closest relative species, T. rangeli, and the distant related T. b. brucei. (A) Network of 33 amino acid predicted sequences constructed using the Neighbour-Net algorithm excluding all conserved sites and with Uncorrected p-distance. The numbers in nodes correspond to bootstrap values from 100 replicates. (B) Polymorphism on cruzipain amino acid sequences from the distinct trypanosome species.
Mentions: To study the relationships of cruzipain genes from all T. cruzi DTUs, T. c. marinkellei and T. dionisii, and homologues from T. rangeli and T. b. brucei (Table 1), we aligned ∼500 bp cdCATL sequences obtained in this study with the corresponding genes from T. cruzi CL Brener (Esmeraldo-like and non-Esmeraldo-like haplotypes), Esmeraldo cl3, JR cl4, M6241 cl6 and Sylvio X10.6. The analyses of either amino acid (Fig. 3) or nucleotide sequences (data not shown) generated networks of cruzipain genes with similar topologies. Sequences of cd-cruzipain from all T. cruzi DTUs always clustered together in a homogeneous assemblage (∼1.2% amino acid sequence divergence) separated from T. c marinkellei (5.5% divergence), and largely divergent from the cluster formed by T. dionisii from Brazil (20%) and Europe (21%). Amino acid sequences of cruzipain genes of all Schizotrypanum species clustered together and largely separated (28%) from the homologous genes of T. rangeli and T. b. brucei (Fig. 3; Table 1).

Bottom Line: In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species.Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs.Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, ICB, Universidade de São Paulo, São Paulo, São Paulo, Brasil.

ABSTRACT
Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches.

Show MeSH
Related in: MedlinePlus