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Genomic analyses, gene expression and antigenic profile of the trans-sialidase superfamily of Trypanosoma cruzi reveal an undetected level of complexity.

Freitas LM, dos Santos SL, Rodrigues-Luiz GF, Mendes TA, Rodrigues TS, Gazzinelli RT, Teixeira SM, Fujiwara RT, Bartholomeu DC - PLoS ONE (2011)

Bottom Line: We demonstrated that all seven groups represented in the array are antigenic.A highly reactive peptide occurs in sixty TcS proteins including members of two new groups and may contribute to the known cross-reactivity of T. cruzi epitopes during infection.Taken together, our results contribute to a better understanding of the real complexity of the TcS family and open new avenues for investigating novel roles of this family during T. cruzi infection.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

ABSTRACT
The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a highly debilitating human pathology that affects millions of people in the Americas. The sequencing of this parasite's genome reveals that trans-sialidase/trans-sialidase-like (TcS), a polymorphic protein family known to be involved in several aspects of T. cruzi biology, is the largest T. cruzi gene family, encoding more than 1,400 genes. Despite the fact that four TcS groups are well characterized and only one of the groups contains active trans-sialidases, all members of the family are annotated in the T. cruzi genome database as trans-sialidase. After performing sequence clustering analysis with all TcS complete genes, we identified four additional groups, demonstrating that the TcS family is even more heterogeneous than previously thought. Interestingly, members of distinct TcS groups show distinctive patterns of chromosome localization. Members of the TcSgroupII, which harbor proteins involved in host cell attachment/invasion, are preferentially located in subtelomeric regions, whereas members of the largest and new TcSgroupV have internal chromosomal locations. Real-time RT-PCR confirms the expression of genes derived from new groups and shows that the pattern of expression is not similar within and between groups. We also performed B-cell epitope prediction on the family and constructed a TcS specific peptide array, which was screened with sera from T. cruzi-infected mice. We demonstrated that all seven groups represented in the array are antigenic. A highly reactive peptide occurs in sixty TcS proteins including members of two new groups and may contribute to the known cross-reactivity of T. cruzi epitopes during infection. Taken together, our results contribute to a better understanding of the real complexity of the TcS family and open new avenues for investigating novel roles of this family during T. cruzi infection.

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Distribution of each TcS group along the T. cruzi chromosomes.(A) Histograms showing the frequency of the TcS genes along the chromosomes. The length of all chromosomes was normalized as 1. The relative position of each gene was calculated by dividing the coordinate of the first nucleotide of the open reading frame by the length of the chromosome. (B) Representation of each group in Figure 1, showing the genes that localize in telomeric regions (black dots for the TcSgroupV and red dots for the other TcS groups). TcSgroupI - blue; TcSgroupII - dark green; TcSgroupIII - light blue; TcSgroupIV - magenta; TcSgroupV - red; TcSgroupIV - gray; TcSgroupVII - orange and TcSgroupVIII - purple. (C) Histogram showing the distribution of TcS pseudogenes along the T. cruzi chromosomes.
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pone-0025914-g004: Distribution of each TcS group along the T. cruzi chromosomes.(A) Histograms showing the frequency of the TcS genes along the chromosomes. The length of all chromosomes was normalized as 1. The relative position of each gene was calculated by dividing the coordinate of the first nucleotide of the open reading frame by the length of the chromosome. (B) Representation of each group in Figure 1, showing the genes that localize in telomeric regions (black dots for the TcSgroupV and red dots for the other TcS groups). TcSgroupI - blue; TcSgroupII - dark green; TcSgroupIII - light blue; TcSgroupIV - magenta; TcSgroupV - red; TcSgroupIV - gray; TcSgroupVII - orange and TcSgroupVIII - purple. (C) Histogram showing the distribution of TcS pseudogenes along the T. cruzi chromosomes.

Mentions: It is known that TcS genes can be found in T. cruzi subtelomeric regions or in internal positions in the chromosomes that are associated with other genes that encode surface proteins [2]. Subtelomeric regions are defined here as sequences extending from the telomeric hexamer repeats to the first nonrepetitive sequence. We investigated whether there is any bias on the chromosome localization of the TcS clusters. Figure 3 shows the chromosomal distribution of the TcS groups. A total of 60 complete TcS genes (not including partial or pseudogenes) can be found associated with the subtelomeric regions. One of them belongs to the brown cluster, which, as mentioned above, was excluded from our analysis. The majority of the subtelomeric TcS genes (36 members, 61%) belongs to TcSgroupII (dark green), 7 members from TcSgroupIV (magenta) and 10 from TcSgroupVIII (purple) (Figures 3 and 4). No TcSgroupIII (light blue) or TcSgroupVI (gray) genes are located at these regions. Interestingly, with one exception, all members of the largest TcS cluster (TcSgroup V, red) are at internal locations in the chromosomes (Figures 3, 4A and 4B). We have also found that the subtelomeric regions are enriched for TcS pseudogenes (Figure 4C), which is in agreement with the hypothesis that these regions were subject to intense rearrangement [54].


Genomic analyses, gene expression and antigenic profile of the trans-sialidase superfamily of Trypanosoma cruzi reveal an undetected level of complexity.

Freitas LM, dos Santos SL, Rodrigues-Luiz GF, Mendes TA, Rodrigues TS, Gazzinelli RT, Teixeira SM, Fujiwara RT, Bartholomeu DC - PLoS ONE (2011)

Distribution of each TcS group along the T. cruzi chromosomes.(A) Histograms showing the frequency of the TcS genes along the chromosomes. The length of all chromosomes was normalized as 1. The relative position of each gene was calculated by dividing the coordinate of the first nucleotide of the open reading frame by the length of the chromosome. (B) Representation of each group in Figure 1, showing the genes that localize in telomeric regions (black dots for the TcSgroupV and red dots for the other TcS groups). TcSgroupI - blue; TcSgroupII - dark green; TcSgroupIII - light blue; TcSgroupIV - magenta; TcSgroupV - red; TcSgroupIV - gray; TcSgroupVII - orange and TcSgroupVIII - purple. (C) Histogram showing the distribution of TcS pseudogenes along the T. cruzi chromosomes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198458&req=5

pone-0025914-g004: Distribution of each TcS group along the T. cruzi chromosomes.(A) Histograms showing the frequency of the TcS genes along the chromosomes. The length of all chromosomes was normalized as 1. The relative position of each gene was calculated by dividing the coordinate of the first nucleotide of the open reading frame by the length of the chromosome. (B) Representation of each group in Figure 1, showing the genes that localize in telomeric regions (black dots for the TcSgroupV and red dots for the other TcS groups). TcSgroupI - blue; TcSgroupII - dark green; TcSgroupIII - light blue; TcSgroupIV - magenta; TcSgroupV - red; TcSgroupIV - gray; TcSgroupVII - orange and TcSgroupVIII - purple. (C) Histogram showing the distribution of TcS pseudogenes along the T. cruzi chromosomes.
Mentions: It is known that TcS genes can be found in T. cruzi subtelomeric regions or in internal positions in the chromosomes that are associated with other genes that encode surface proteins [2]. Subtelomeric regions are defined here as sequences extending from the telomeric hexamer repeats to the first nonrepetitive sequence. We investigated whether there is any bias on the chromosome localization of the TcS clusters. Figure 3 shows the chromosomal distribution of the TcS groups. A total of 60 complete TcS genes (not including partial or pseudogenes) can be found associated with the subtelomeric regions. One of them belongs to the brown cluster, which, as mentioned above, was excluded from our analysis. The majority of the subtelomeric TcS genes (36 members, 61%) belongs to TcSgroupII (dark green), 7 members from TcSgroupIV (magenta) and 10 from TcSgroupVIII (purple) (Figures 3 and 4). No TcSgroupIII (light blue) or TcSgroupVI (gray) genes are located at these regions. Interestingly, with one exception, all members of the largest TcS cluster (TcSgroup V, red) are at internal locations in the chromosomes (Figures 3, 4A and 4B). We have also found that the subtelomeric regions are enriched for TcS pseudogenes (Figure 4C), which is in agreement with the hypothesis that these regions were subject to intense rearrangement [54].

Bottom Line: We demonstrated that all seven groups represented in the array are antigenic.A highly reactive peptide occurs in sixty TcS proteins including members of two new groups and may contribute to the known cross-reactivity of T. cruzi epitopes during infection.Taken together, our results contribute to a better understanding of the real complexity of the TcS family and open new avenues for investigating novel roles of this family during T. cruzi infection.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

ABSTRACT
The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a highly debilitating human pathology that affects millions of people in the Americas. The sequencing of this parasite's genome reveals that trans-sialidase/trans-sialidase-like (TcS), a polymorphic protein family known to be involved in several aspects of T. cruzi biology, is the largest T. cruzi gene family, encoding more than 1,400 genes. Despite the fact that four TcS groups are well characterized and only one of the groups contains active trans-sialidases, all members of the family are annotated in the T. cruzi genome database as trans-sialidase. After performing sequence clustering analysis with all TcS complete genes, we identified four additional groups, demonstrating that the TcS family is even more heterogeneous than previously thought. Interestingly, members of distinct TcS groups show distinctive patterns of chromosome localization. Members of the TcSgroupII, which harbor proteins involved in host cell attachment/invasion, are preferentially located in subtelomeric regions, whereas members of the largest and new TcSgroupV have internal chromosomal locations. Real-time RT-PCR confirms the expression of genes derived from new groups and shows that the pattern of expression is not similar within and between groups. We also performed B-cell epitope prediction on the family and constructed a TcS specific peptide array, which was screened with sera from T. cruzi-infected mice. We demonstrated that all seven groups represented in the array are antigenic. A highly reactive peptide occurs in sixty TcS proteins including members of two new groups and may contribute to the known cross-reactivity of T. cruzi epitopes during infection. Taken together, our results contribute to a better understanding of the real complexity of the TcS family and open new avenues for investigating novel roles of this family during T. cruzi infection.

Show MeSH
Related in: MedlinePlus