Trypanosoma cruzi: Sequence polymorphism of the gene encoding the Tc52 immunoregulatory-released factor in relation to the phylogenetic diversity of the species

Oury, Bruno; Tarrieu, Frédérique; Monte-Alegre, Adriano Figueiredo; Ouaissi, Ali

doi:10.1016/j.exppara.2005.07.001

Cited by 11 publications

(10 citation statements)

References 34 publications

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“…The two sequences from CL Brener also correspond to both alleles of an heterozygous genotype (DTU IIe). Out of 445 amino acids, 40 amino acid substitutions between clones were recorded, including the new substitutions observed in the N-terminal and C-terminal parts of the protein that were not sequenced in the previous study on Tc52 gene polymorphisms (Oury et al 2005). The distribution of these mutations is consistent with the T. cruzi lineages and the genetic subdivisions in DTUs.…”

Section: Interstrain Variability Of Tc52 Sequencesmentioning

confidence: 93%

“…Strains from lineage I are homogeneous, while strains from lineage II exhibit inter-DTU mutations that are also consistent with the hybrid genotypes of DTUs IId and IIe. We observed two mutations in the putative amino acids involved in GSH binding or enzymatic function, deduced from homologous comparison with human and rat GSTs (Oury et al 2005). Amino acid 11 (Leu or Ile for Met) corresponds to one of the sites involved in GSH binding.…”

Section: Interstrain Variability Of Tc52 Sequencesmentioning

confidence: 95%

“…Further, monoallelic disruption of Tc52 results in an attenuated parasite clone (Tc52+/−) displaying an impaired metacyclogenesis, a lower virulence in vitro and in vivo (Allaoui et al 1999) and no significant immunosuppression in mouse infection, when compared with the wild-type parental clone (Garzon et al 2003). Partial sequencing of the Tc52 gene in various T. cruzi strains identified mutations between strains, a few of which in the putative amino acids involved in glutathione (GSH) binding or enzyme activity (Oury et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Sequence diversity and differential expression of Tc52 immuno-regulatory protein in Trypanosoma cruzi: potential implications in the biological variability of strains

Mathieu-Daudé¹,

Bosseno²,

Garzón³

et al. 2007

Parasitol Res

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Trypanosoma cruzi is highly heterogeneous in terms of genetics and biological properties. To explore the diversity of T. cruzi, we focused our study on the T. cruzi Tc52 protein playing a critical immunosuppressive role during infection. Sequence variability and expression levels of this virulence factor were analysed in various strains. Among the 40 amino acid substitutions detected in the Tc52 coding sequences, three substitutions may have an impact on protein activity or function, as two are localized in sites involved in the glutathione binding and the third is present in the region bearing immunomodulatory function. This sequence variability was consistent with the genetic subdivisions of T. cruzi. Moreover, we observed that the level of Tc52 transcripts and proteins varied between the different strains, but we did not find a significant correlation between Tc52 expression and the phylogeny of the parasite. Thus, both diversity in the sequences and differences in the expression levels of Tc52 protein may be involved in the biological variability of T. cruzi, especially in virulence and immunosuppression properties of T. cruzi strains.

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Section: Interstrain Variability Of Tc52 Sequencesmentioning

confidence: 93%

Section: Interstrain Variability Of Tc52 Sequencesmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Sequence diversity and differential expression of Tc52 immuno-regulatory protein in Trypanosoma cruzi: potential implications in the biological variability of strains

Mathieu-Daudé¹,

Bosseno²,

Garzón³

et al. 2007

Parasitol Res

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“…PCR amplification with GoTaq Taq polymerase (Promega Corporation, Madison, WI) was completed for the four gene targets, MSH2 , Tc52 , DHFR-TS , and COII-ND1 , following the respective previously published protocols [27], [28], [10]. DNA extraction, amplification, and product analysis were performed in separate dedicated laboratory areas.…”

Section: Methodsmentioning

confidence: 99%

Genetic Variation and Exchange in Trypanosoma cruzi Isolates from the United States

et al. 2013

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Trypanosoma cruzi, the causative agent of Chagas disease, is a multiclonal parasite with high levels of genetic diversity and broad host and geographic ranges. Molecular characterization of South American isolates of T. cruzi has demonstrated homologous recombination and nuclear hybridization, as well as the presence of 6 main genetic clusters or “discrete typing units” (DTUs). Few studies have extensively investigated such exchange events and genetic diversity in North American isolates. In the current study, we genetically characterized over 50 US isolates from wildlife reservoirs (e.g., raccoons, opossums, armadillos, skunks), domestic dogs, humans, nonhuman primates, and reduviid vectors from nine states (TX, CA, OK, SC, FL, GA, MD, LA, TN) using a multilocus sequencing method. Single nucleotide polymorphisms were identified in sequences of the mismatch-repair class 2 (MSH2) and Tc52 genes. Typing based on the two genes often paralleled genotyping by classic methodologies using mini-exon and 18S and 24Sα rRNA genes. Evidence for genetic exchange was obtained by comparing sequence phylogenies of nuclear and mitochondrial gene targets, dihydrofolate reductase-thymidylate synthase (DHFR-TS) and the cytochrome oxidase subunit II- NADH dehydrogenase subunit I region (COII-ND1), respectively. We observed genetic exchange in several US isolates as demonstrated by incongruent mitochondrial and nuclear genes phylogenies, which confirms a previous finding of a single genetic exchange event in a Florida isolate. The presence of SNPs and evidence of genetic exchange illustrates that strains from the US are genetically diverse, even though only two phylogenetic lineages have been identified in this region.

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“…Tc52 is crucial for the survival of the parasite as the knockout of both alleles is lethal (20). Tc52 is also highly conserved, with the presence of single nucleotide polymorphisms (SNPs) between some strains, and its expres-sion was demonstrated in different strains of T. cruzi (21)(22)(23)(24). All of these characteristics make Tc52 a promising vaccine candidate.…”

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confidence: 99%

Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge

et al. 2014

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In this work we immunized mice with DNA encoding full-length Tc52 or its amino-or carboxy-terminal (N-and C-term, respectively) domain carried by attenuated Salmonella as a DNA delivery system. As expected, Salmonella-mediated DNA delivery resulted in low antibody titers and a predominantly Th1 response, as shown by the ratio of IgG2a/IgG1-specific antibodies. Despite modest expression of Tc52 in trypomastigotes, the antibodies elicited by vaccination were able to mediate lysis of the trypomastigotes in the presence of complement and inhibit their invasion of mammal cells in vitro. The strongest functional activity was observed with sera from mice immunized with Salmonella carrying the N-term domain (SN-term), followed by Tc52 (STc52), and the C-term domain (SC-term). All immunized groups developed strong cellular responses, with predominant activation of Th1 cells. However, mice immunized with SN-term showed higher levels of interleukin-10 (IL-10), counterbalancing the inflammatory reaction, and also strong activation of Tc52-specific gamma interferon-positive (IFN-␥ ؉ ) CD8 ؉ T cells. In agreement with this, although all prototypes conferred protection against infection, immunization with SN-term promoted greater protection than that with SC-term for all parameters tested and slightly better protection than that with STc52, especially in the acute stage of infection. We conclude that the N-terminal domain of Tc52 is the section of the protein that confers maximal protection against infection and propose it as a promising candidate for vaccine development.

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Trypanosoma cruzi: Sequence polymorphism of the gene encoding the Tc52 immunoregulatory-released factor in relation to the phylogenetic diversity of the species

Cited by 11 publications

References 34 publications

Sequence diversity and differential expression of Tc52 immuno-regulatory protein in Trypanosoma cruzi: potential implications in the biological variability of strains

Sequence diversity and differential expression of Tc52 immuno-regulatory protein in Trypanosoma cruzi: potential implications in the biological variability of strains

Genetic Variation and Exchange in Trypanosoma cruzi Isolates from the United States

Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge

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