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

Abstract

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.

Fig. 1:. the 24Sα rRNA gene sequence and the intergenic region of the mini-exon gene are valuable markers to genotype Trypanosoma cruzi isolates. Schematic representation of T. cruzi Ribosomal RNA cistron and Mini exon genes. The arrows indicate the position of primers used for polymerase chain reaction (PCR) amplification of gene regions. The amplification products for different discrete typing units (DTUs) after gel electrophoresis are shown.

Fig. 2:. sylvatic reservoirs of Trypanosoma cruzi discrete typing units (DTUs). The figure illustrates the consensus of the preferential, but not exclusive, association of DTUs to certain species / orders of wild mammals. Created with Biorender.com.

Fig. 3:. map shows prevalence of human Trypanosoma cruzi discrete typing units (DTUs) in Mexico and countries of Central and South America. The sizes of the parasite drawings reflect the relative occurrence of the DTUs in a given area (the larger, the more prevalent). The dashed line separates the geographical regions according to the prevalent chronic Chagas disease pathology: chronic Chagas cardiomyopathy (CCC) and digestive form (DIG).

Fig. 4:. diversity of multigene families encoding surface proteins among Trypanosoma cruzi discrete typing units (DTUs) and parasite adaptability to different hosts and environments. T. cruzi genome is compartmentalised into the core and disruptive regions. The core compartment encodes conserved proteins mainly associated to house-keeping functions, while the disruptive compartment contains multicopy genes encoding polymorphic surface proteins, such as TS, MASP, and mucin, that display impressive intragenomic and inter-DTU sequence variability. These genes families are involved in several host-parasite interactions that may contribute to T. cruzi establishing the infection in different host cells and mammals and explore distinct niches. The coloured horizontal bars and number ranges represent the gene copy numbers of each family among strains of distinct DTUs. DTUs commonly associated to human (TcI, II, IV and V), vectors (all DTUs), and reservoirs (TcI, II, III and IV) infections are depicted in the circles at the bottom. Created with Biorender.com.