Fifteen Years after the Definition of Trypanosoma cruzi DTUs: What Have We Learned?

Abstract

Trypanosoma cruzi, the protozoan causative of Chagas disease (ChD), exhibits striking genetic and phenotypic intraspecific diversity, along with ecoepidemiological complexity. Human-pathogen interactions lead to distinct clinical presentations of ChD. In 2009, an international consensus classified T. cruzi strains into six discrete typing units (DTUs), TcI to TcVI, later including TcBat, and proposed reproducible genotyping schemes for DTU identification. This article aims to review the impact of classifying T. cruzi strains into DTUs on our understanding of biological, ecoepidemiological, and pathogenic aspects of T. cruzi. We will explore the likely origin of DTUs and the intrinsic characteristics of each group of strains concerning genome organization, genomics, and susceptibility to drugs used in ChD treatment. We will also provide an overview of the association of DTUs with mammalian reservoirs, and summarize the geographic distribution, and the clinical implications, of prevalent specific DTUs in ChD patients. Throughout this review, we will emphasize the crucial roles of both parasite and human genetics in defining ChD pathogenesis and chemotherapy outcome.

Keywords: Chagas disease manifestations; Trypanosoma cruzi; discrete typing units; ecoepidemiology; genomics.

Figure 1

Molecular karyotype of T. cruzi strains representative of four DTUs: TcVI (CL Brener), TcII (Esmeraldo cl3 and Y), TcV (NRcl3, SO3 cl5, and Sc43 cl1), and TcI (Silvio X10 cl1, Dm28c and YuYu). (A) Chromosomal DNA was separated by PFGE and stained with ethidium bromide. After transfer to Zeta-Probe membranes, the blot was hybridized with 32P-labeled probes corresponding to (B) DNA repetitive sequences E12 and 195-bp satellite DNA; and (C) single copy genes B13, B12, and HSP70. See experimental details in [51]. M = Molecular size markers. Reprinted/adapted with permission from Ref. [51]. 2004, Elsevier.

Figure 2

Distribution of T. cruzi DTUs in the sylvatic and domestic cycles of transmission. The figure illustrates the consensus of the preferential, but not exclusive, association of DTUs to certain species/orders of wild mammals. In the domestic cycle, the DTUs prevalent in humans are indicated.