Multiple Trypanosoma cruzi antigens containing tandemly repeated amino acid sequence motifs

Ibáñez, Carlos F.; Affranchino, José L.; Macina, Roberto A.; Reyes, María B.; Leguizamon, Susana; Camargo, M. E.; Åslund, Lena; Pettersson, Ulf; Frasch, Alberto C.C.

doi:10.1016/0166-6851(88)90129-6

Cited by 135 publications

(83 citation statements)

References 16 publications

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“…These observations contribute to the emerging overall picture that the host antibody response both in the African trypanosomiases as well as in South American Chagas disease is strongly directed against parasite proteins which have the common denominators of being (i) very large and (ii) highly internally repetitive with a very high degree of sequence conservation between the individual repeat units (Ibanez et al 1988;Hoft et al 1989;Lafaille et al 1989;Duncan, Gay & Donelson, 1991;Pollevick et al 1991;Burns et al 1993). In addition, all these antigenic proteins are intracellular proteins, with the exception of SAPA, which is a GPI-anchored surface protein (Pollevick et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Repetitive proteins from the flagellar cytoskeleton of African trypanosomes are diagnostically useful antigens

et al. 1995

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SUMMARYTrypanosome infection of mammalian hosts leads, within days, to a strong early response against a small, distinct number of parasite proteins. One of these proteins is the variable surface glycoprotein (VSG). Most of the others are apparently non-variable, intracellular trypanosome proteins. Two of these antigens I 2 and I 17 are now characterized at the molecular level. Both exhibit a highly repetitive amino acid sequence organization, but they show no sequence similarity either to each other or to any other proteins known to date. Preliminary serological analyses indicate that both allow the early, sensitive and specific detection of infections with different species of trypanosomatids, making them interesting candidates for the development of diagnostic tools for trypanosomiasis detection.

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Section: Discussionmentioning

confidence: 99%

Repetitive proteins from the flagellar cytoskeleton of African trypanosomes are diagnostically useful antigens

et al. 1995

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“…Although their exact function is still unclear, it has been suggested that they are involved in protein-protein interactions, binding to host-cell receptors or other processes. A relevant feature concerning protein repeats is the presence of substantial humoral response that barely confer a protective immunity (19,20), which leads to the speculation that these could be decoy or immunomodulatory moieties (15,18,21,22). Although the Bmpredicted proteome (11,610 proteins) has an overall occurrence of TRs of approximately 15% (i.e., using a threshold of six or more residues occurring twice or more in a given protein; SI Appendix, Table S7), it does not appear that the presence of TR in proteins is related to the humoral responses they engender.…”

Section: Resultsmentioning

confidence: 99%

“…(16), and Trypanosome spp. (17,18), is widespread. Although their exact function is still unclear, it has been suggested that they are involved in protein-protein interactions, binding to host-cell receptors or other processes.…”

Section: Resultsmentioning

confidence: 99%

Stage-specific proteomic expression patterns of the human filarial parasiteBrugia malayiand its endosymbiontWolbachia

Bennuru

Meng

Ribeiro

et al. 2011

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

123

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Global proteomic analyses of pathogens have thus far been limited to unicellular organisms (e.g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e.g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of Brugia malayi, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of Wolbachia, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as "hypothetical," the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix proteins and those with immunologic effects as enriched in the microfilarial and L3 stages. Parasite sex-and stage-specific protein expression identified those pathways related to parasite differentiation and demonstrates stage-specific expression by the Bm endosymbiont Wolbachia as well.filaria | nematode D isease associated with infection by Brugia malayi (Bm) and Wuchereria bancrofti, the two major causative organisms of human lymphatic filariasis, is the second leading cause of morbidity/disability worldwide, in large part because of the parasites' ability to alter the structural and functional integrity of the lymphatics, leading to lymphedema and elephantiasis. Invasion, establishment of infection within the host and development are essential processes within the complex parasite life cycle (SI Appendix, Fig. S1), with many of the parasitic stages being targets for therapeutic intervention or vaccines. Each of the filarial life cycle stages has characteristics that are shared and others that are stage-specific.Filarial infections are often characterized by a series of discrete host responses directed at the parasite and its endosymbiont Wolbachia that evolve during the course of infection. Because proteins are usually the effectors of most biological functions, proteomic data enable a more direct understanding of these important processes compared with those inferred from genomic studies. Absolute quantification of genome-wide expressed proteins is not yet within our reach for most eukaryotes. However, spectral counts of massive MS-based data (e.g., observed frequencies of each peptide) allow for relative quantification. Proteomic data also allow for clearer genomic curation by improving annotation and the identification of translational sites, stop codon read-throughs, frame shifts, and predict...

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“…Restriction analysis of genomic DNA confirmed the repetitive structure of the GM6 gene(s) and indicated that GM6 is coded for by a very large gene which consists predominantly of the repetitive 204 bp motif (unpublished observations). Database searching with the GM6 amino acid sequence revealed considerable similarity with an antigen from T. cruzi which had been isolated by immunoscreening with infected patient sera (antigen 1, Ibanez et al 1988). Antigen 1 from T. cruzi and GM6 from T. b. gambiense both consist of conserved 68 amino acid repeat units and they share 50% similarity (Fig.…”

Section: Gm6 Is a Repetitive Antigen With Sequence Similarity To T Cmentioning

confidence: 98%

Identification and characterization of two repetitive non-variable antigens from African trypanosomes which are recognized early during infection

et al. 1992

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SUMMARYThe present paper describes two repetitive proteins representing common antigens of African trypanosomes which are non-variant and which are recognized early in infection by the host immune system. These antigens were identified by their ability to immunoreact with bovine serum taken during the early phase of a cyclic trypanosomal infection. Screening of a cDNA library from T. b. gambiense with such early infection serum identified a protein which contains a repetitive motif consisting of 68 amino acid repeat units (GM6). Immunofluorescence and immunogold electron microscopy revealed that GM6 is located on fibres which connect the microtubules of the membrane skeleton with the flagellum. A second repetitive antigen detected by this serum is MARP1 (microtubule-associated repetitive protein 1), a protein previously characterized in this laboratory as a high-molecular weight component of the membrane skeleton, which consists of more than 50 tandemly repeated, near-identical 38 amino acid repeat units. Beta-galactosidase fusion products of both proteins demonstrated a strong immunoreactivity with sera from T. b. brucei and T. congolense-infected cattle. The result from this preliminary immunological evaluation indicates a high immunodiagnostic sensititivy (90%) of the two recombinant antigens which make them interesting candidates for immunodiagnosis of trypanosomiasis in cattle.

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Multiple Trypanosoma cruzi antigens containing tandemly repeated amino acid sequence motifs

Cited by 135 publications

References 16 publications

Repetitive proteins from the flagellar cytoskeleton of African trypanosomes are diagnostically useful antigens

Repetitive proteins from the flagellar cytoskeleton of African trypanosomes are diagnostically useful antigens

Stage-specific proteomic expression patterns of the human filarial parasiteBrugia malayiand its endosymbiontWolbachia

Identification and characterization of two repetitive non-variable antigens from African trypanosomes which are recognized early during infection

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