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Study Finds Proteomic Patterns Coincide with Sub-Species Phylogeny for Chagas Disease Parasite

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – The protein repertoire for the Chagas disease-causing protozoan Trypanosoma cruzi varies with the parasite's sub-species phylogeny, according to a study appearing online last night in the Proceedings of the National Academy of Science.

Researchers from France, Canada, and the US used fluorescence difference gel electrophoresis and mass spectrometry to do proteomic analyses on dozens of T. cruzi stocks with known phylogeny, looking at how sub-species relationships related to protein patterns in the parasite. Indeed, proteomic profiles appeared to coincide with phylogeny in the Chagas-causing pathogen, hinting that protein content may serve as a tool for distinguishing parasites and tracking biological pathways that are active in particular parasites.

"Our study establishes a definite link between T. cruzi phylogenetic diversity and quantified proteomic expression," lead author Jenny Telleria, a researcher with the Institut de Recherche pour le Developpement, and co-authors wrote. "Our results suggest that some proteins, or their differential levels of expression, could be specifically associated with different [discrete typing units]."

Chagas disease is an infectious disease that can be spread by insects or blood transfusions. Early forms of the infection are characterized by symptoms such as fever, rash, or facial swelling. Untreated, the disease may lead to heart, digestive, or nervous system problems, the researchers explained.

In 2005, an international research group reported in Science that they had sequenced the genome of the Chagas-causing parasite T. cruzi, facilitating the discovery of nearly 22,600 predicted proteins in the parasite.

Although functional information is available for roughly half of these proteins, Telleria and colleagues noted, many proteins have functions that are still unknown.

In an effort to explore potential relationships between T. cruzi sub-species phylogeny and protein profiles, the researchers decided to do a proteomic study of T. cruzi stocks with known phylogenetic relationships.

Using a combination of 2-D fluorescence difference gel electrophoresis and mass spectrometry, the team first looked at proteomic profiles in nine T. cruzi stocks that had been phylogenetically characterized using multi-locus enzyme electrophoresis marker data at 22 loci. They then expanded their analysis to include 26 stocks.

The researchers found evidence that proteome patterns correspond to phylogeny in T. cruzi, with parasites from different genetic sub-groups — known as discrete typing units — sharing some protein patterns.

"Although the phylogenetic tree and the proteomic dendrogram are not precisely coincident with the 26 stocks, the correlation between genetic and proteomic distances remains highly significant, which clearly indicates that the evolution of genetic and proteomic characters are far from being independent," the researchers wrote.

Moreover, the team narrowed in on nine protein sites that significantly differed from one discrete typing unit to the next, including several structural proteins, as well as stress and metabolic proteins.

Based on their findings so far, the researchers suggested that protein information could potentially serve as a tool for gleaning information about pathogenicity and other clinical characteristics. And, they argued, "Our data might provide significant information for identifying drug or vaccine targets specific for given T. cruzi genotypes."

"[W]e are proposing proteomics as an informative biomarker because it could reveal processes involved in different biological pathways of the parasite," the team concluded. "Broadening the current focus of research so as to include other proteins that might be differentially expressed in different [discrete typing units] might conceivably lead to new specific therapies associated with T. cruzi phylogenetic diversity."

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