Trypanosoma cruzi genetic diversity: impact on transmission cycles and Chagas disease

Trypanosoma cruzi, the agent of Chagas disease (ChD), exhibits remarkable biological and genetic diversity, along with eco-epidemiological complexity. In order to facilitate communication among researchers aiming at the characterisation of biological and epidemiological aspects of T. cruzi, parasite isolates and strains were partitioned into seven discrete typing units (DTUs), TcI-TcVI and TcBat, identifiable by reproducible genotyping protocols. Here we present the potential origin of the genetic diversity of T. cruzi and summarise knowledge about eco-epidemiological associations of DTUs with mammalian reservoirs and vectors. Circumstantial evidence of a connection between T. cruzi genotype and ChD manifestations is also discussed emphasising the role of the host's immune response in clinical ChD progression. We describe genomic aspects of DTUs focusing on polymorphisms in multigene families encoding surface antigens that play essential functions for parasite survival both in the insect vector and the mammalian host. Such antigens most probably contributed to the parasite success in establishing infections in different hosts and exploring several niches. Gaps in the current knowledge and challenges for future research are pointed out.

Vibrio sp. ArtGut-C1, a polyhydroxybutyrate producer isolated from the gut of the aquaculture live diet Artemia (Crustacea)

BACKGROUND: Vibrio species display variable and plastic fitness strategies to survive and interact with multiple hosts, including marine aquaculture species that are severely affected by pathogenic Vibrios. The culturable Vibrio sp. strain ArtGut-C1, the focus of this study, provides new evidence of such phenotypic plasticity as it accumulates polyhydroxybutyrate (PHB), a biodegradable polymer with anti-pathogen activity, particularly in the marine larviculture phase. The strain was isolated from the gut of laboratory-reared Artemia individuals, the live diet and PHB carrier used in larviculture. Its main phenotypic properties, taxonomic status and genomic properties are reported based on the whole-genome sequencing. RESULTS: Vibrio sp. ArtGut-C1 yielded 72.6% PHB of cells' dry weight at 25 C. The genomic average nucleotide identity (ANI) shows it is closely related to V. diabolicus (ANI: 88.6%). Its genome contains 5,236,997- bp with 44.8% GC content, 3,710 protein-coding sequences, 96 RNA, 9 PHB genes functionally related to PHB metabolic pathways, and several genes linked to competing and colonizing abilities. CONCLUSIONS: This culturable PHB-accumulating Vibrio strain shows high genomic and phenotypic variability. It may be used as a natural pathogen biocontrol in the marine hatchery and as a potential cell factory for PHB production.

The fallacy of racial pharmacogenomics

Personalized pharmacogenomics aims to use individual genotypes to direct medical treatment. Unfortunately, the loci relevant for the pharmacokinetics and especially the pharmacodynamics of most drugs are still unknown. Moreover, we still do not understand the role that individual genotypes play in modulating the pathogenesis, the clinical course and the susceptibility to drugs of human diseases which, although appearing homogeneous on the surface, may vary from patient to patient. To try to deal with this situation, it has been proposed to use interpopulational variability as a reference for drug development and prescription, leading to the development of "race-targeted drugs". Given the present limitations of genomic knowledge and of the tools needed to fully implement it today, some investigators have proposed to use racial criteria as a palliative measure until personalized pharmacogenomics is fully developed. This was the rationale for the FDA approval of BiDil for treatment of heart failure in African Americans. I will evaluate the efficacy and safety of racial pharmacogenomics here and conclude that it fails on both counts. Next I shall review the perspectives and the predicted rate of development of clinical genomic studies. The conclusion is that "next-generation" genomic sequencing is advancing at a tremendous rate and that true personalized pharmacogenomics, based on individual genotyping, should soon become a clinical reality.