Virulence in Trypanosoma cruzi infection correlates with the expression of a distinct family of sialidase superfamily genes

Weston, David S.; Patel, Bhavesha; Voorhis, Wesley C. Van

doi:10.1016/s0166-6851(98)00152-2

Cited by 47 publications

(27 citation statements)

References 20 publications

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“…These enzymes may be virulence factors; and they participate in binding to noninfected epithelial, fibroblast, and muscle mammalian cell lines (9,24). They are strong immunogens that elicit polyclonal antibody responses and are implicated in the induction of both inflammation and autoimmunity (21,30). A monoclonal antibody (monoclonal antibody 39) that recognizes parasite transialidases detects polypeptide bands ranging in size from 85 to 170 kDa in TESA proteins (23).…”

Section: Discussionmentioning

confidence: 99%

Purified Excreted-Secreted Antigens from Trypanosoma cruzi Trypomastigotes as Tools for Diagnosis of Chagas' Disease

et al. 2006

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There is currently no "gold standard" test for the diagnosis of late-stage Chagas' disease. As a result, protection of the blood supply in areas where Chagas' disease is endemic remains problematic. A panel of 709 serum samples from subjects with confirmed Chagas' disease (n ‫؍‬ 195), healthy controls (n ‫؍‬ 400), and patients with other parasitic diseases (n ‫؍‬ 114) was used to assess enzyme-linked immunosorbent assays (ELISAs) based on a concentrated extract of excretory-secretory antigens from either Brazil or Tulahuen strain Trypanosoma cruzi trypomastigotes (total trypomastigote excretory-secretory antigens [TESAs]). The total TESA-based assays had excellent overall sensitivity (100%) and specificity (>94%), except for cross-reactivity with Leishmania-infected sera. In an attempt to increase the specificity of the assay, immunoaffinity chromatography was used to purify the TESA proteins (TESA IA proteins). By Western blotting, a series of polypeptide bands with molecular masses ranging from 60 to 220 kDa were recognized by pooled sera positive for Chagas' disease. An ELISA based on TESA IA proteins had a slightly lower sensitivity (98.6%) but an improved specificity (100%) compared to the sensitivity and specificity of the total TESA protein-based ELISAs. A 60-kDa polypeptide was identified as a major contributor to the cross-reactivity with Leishmania. These data suggest the need for field validation studies of TESA-and TESA IA -based assays in regions where Chagas' disease is endemic.

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Section: Discussionmentioning

confidence: 99%

Purified Excreted-Secreted Antigens from Trypanosoma cruzi Trypomastigotes as Tools for Diagnosis of Chagas' Disease

et al. 2006

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“…Interestingly, the latter function is assumed by the most constant regions of SIRE, i.e., its first bases, and region II, respectively. These features of SIRE are important because in T. cruzi the polyadenylation site and surrounding intergenic sequences play a capital role for stage-specific expression of genes (26).…”

Section: Discussionmentioning

confidence: 99%

The short interspersed repetitive element of Trypanosoma cruzi , SIRE, is part of VIPER, an unusual retroelement related to long terminal repeat retrotransposons

Vázquez

Ben‐Dov

Lorenzi

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The short interspersed repetitive element (SIRE) of Trypanosoma cruzi was first detected when comparing the sequences of loci that encode the TcP2␤ genes. It is present in about 1,500 -3,000 copies per genome, depending on the strain, and it is distributed in all chromosomes. An initial analysis of SIRE sequences from 21 genomic fragments allowed us to derive a consensus nucleotide sequence and structure for the element, consisting of three regions (I, II, and III) each harboring distinctive features. Analysis of 158 transcribed SIREs demonstrates that the consensus is highly conserved. The sequences of 51 cDNAs show that SIRE is included in the 3 end of several mRNAs, always transcribed from the sense strand, contributing the polyadenylation site in 63% of the cases. This study led to the characterization of VIPER (vestigial interposed retroelement), a 2,326-bp-long unusual retroelement. VIPER's 5 end is formed by the first 182 bp of SIRE, whereas its 3 end is formed by the last 220 bp of the element. Both SIRE moieties are connected by a 1,924-bp-long fragment that carries a unique ORF encoding a complete reverse transcriptase-RNase H gene whose 15 C-terminal amino acids derive from codons specified by SIRE's region II. The amino acid sequence of VIPER's reverse transcriptaseRNase H shares significant homology to that of long terminal repeat retrotransposons. The fact that SIRE and VIPER sequences are found only in the T. cruzi genome may be of relevance for studies concerning the evolution and the genome flexibility of this protozoan parasite.

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“…Sequencing of BAC clones was performed as recommended on the Institute for Genomic Research website. Rapid amplification of cDNA ends was used to clone the 5Ј-ends of the ␣-and ␤-subunits of PFT (20). First, mRNA was isolated from T. brucei procyclics using the QuickPrep Micro mRNA Purification kit (Amersham Pharmacia Biotech).…”

Section: Methodsmentioning

confidence: 99%

Cloning, Heterologous Expression, and Distinct Substrate Specificity of Protein Farnesyltransferase from Trypanosoma brucei

Buckner¹,

Yokoyama²,

Nguyen³

et al. 2000

Journal of Biological Chemistry

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Protein prenylation occurs in the protozoan that causes African sleeping sickness (Trypanosoma brucei), and the protein farnesyltransferase appears to be a good target for developing drugs. We have cloned the ␣-and ␤-subunits of T. brucei protein farnesyltransferase (TB-PFT) using nucleic acid probes designed from partial amino acid sequences obtained from the enzyme purified from insect stage parasites. TB-PFT is expressed in both bloodstream and insect stage parasites. Enzymatically active TB-PFT was produced by heterologous expression in Escherichia coli. Compared with mammalian protein farnesyltransferases, TB-PFT contains a number of inserts of >25 residues in both subunits that reside on the surface of the enzyme in turns linking adjacent ␣-helices. Substrate specificity studies with a series of 20 peptides SSCALX (where X indicates a naturally occurring amino acid) show that the recombinant enzyme behaves identically to the native enzyme and displays distinct specificity compared with mammalian protein farnesyltransferase. TB-PFT prefers Gln and Met at the X position but not Ser, Thr, or Cys, which are good substrates for mammalian protein farnesyltransferase. A structural homology model of the active site of TB-PFT provides a basis for understanding structureactivity relations among substrates and CAAX mimetic inhibitors.

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Virulence in Trypanosoma cruzi infection correlates with the expression of a distinct family of sialidase superfamily genes

Cited by 47 publications

References 20 publications

Purified Excreted-Secreted Antigens from Trypanosoma cruzi Trypomastigotes as Tools for Diagnosis of Chagas' Disease

Purified Excreted-Secreted Antigens from Trypanosoma cruzi Trypomastigotes as Tools for Diagnosis of Chagas' Disease

The short interspersed repetitive element of Trypanosoma cruzi , SIRE, is part of VIPER, an unusual retroelement related to long terminal repeat retrotransposons

Cloning, Heterologous Expression, and Distinct Substrate Specificity of Protein Farnesyltransferase from Trypanosoma brucei

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