Back to Search
Start Over
Molecular and antigenic characterization of Trypanosoma cruzi TolT proteins.
- Source :
-
PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2019 Mar 14; Vol. 13 (3), pp. e0007245. Date of Electronic Publication: 2019 Mar 14 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Background: TolT was originally described as a Trypanosoma cruzi molecule that accumulated on the trypomastigote flagellum bearing similarity to bacterial TolA colicins receptors. Preliminary biochemical studies indicated that TolT resolved in SDS-PAGE as ~3-5 different bands with sizes between 34 and 45 kDa, and that this heterogeneity could be ascribed to differences in polypeptide glycosylation. However, the recurrent identification of TolT-deduced peptides, and variations thereof, in trypomastigote proteomic surveys suggested an intrinsic TolT complexity, and prompted us to undertake a thorough reassessment of this antigen.<br />Methods/principle Findings: Genome mining exercises showed that TolT constitutes a larger-than-expected family of genes, with at least 12 polymorphic members in the T. cruzi CL Brener reference strain and homologs in different trypanosomes. According to structural features, TolT deduced proteins could be split into three robust groups, termed TolT-A, TolT-B, and TolT-C, all of them showing marginal sequence similarity to bacterial TolA proteins and canonical signatures of surface localization/membrane association, most of which were herein experimentally validated. Further biochemical and microscopy-based characterizations indicated that this grouping may have a functional correlate, as TolT-A, TolT-B and TolT-C molecules showed differences in their expression profile, sub-cellular distribution, post-translational modification(s) and antigenic structure. We finally used a recently developed fluorescence magnetic beads immunoassay to validate a recombinant protein spanning the central and mature region of a TolT-B deduced molecule for Chagas disease serodiagnosis.<br />Conclusion/significance: This study unveiled an unexpected genetic and biochemical complexity within the TolT family, which could be exploited for the development of novel T. cruzi biomarkers with diagnostic/therapeutic applications.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Computational Biology
Glycosylation
Immunoassay
Membrane Proteins classification
Protozoan Proteins classification
Antigens, Protozoan genetics
Antigens, Protozoan immunology
Membrane Proteins genetics
Membrane Proteins immunology
Polymorphism, Genetic
Protozoan Proteins genetics
Protozoan Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-2735
- Volume :
- 13
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PLoS neglected tropical diseases
- Publication Type :
- Academic Journal
- Accession number :
- 30870417
- Full Text :
- https://doi.org/10.1371/journal.pntd.0007245