Beyond the first case of Chagas disease: the Berenice strain as a model for understanding long-term Trypanosoma cruzi infection.

Here, we review the key findings on the genetic characterisation of Berenice strains of Trypanosoma cruzi isolated from a 2-year-old child, Berenice, the first patient with Chagas disease described in the literature in 1909. Be-62 and Be-78 strains were isolated from Berenice when she was 55 and 71 years old, respectively. They were comparatively studied, revealing several important genetic differences that indicated the presence of heterogeneous T. cruzi populations within the infection of patient Berenice. Recently, a high-quality whole-genome assembly was generated using the strain Be-62, which was isolated in 1962. Even after decades-long persistence in the patient, there is a high level of conservation in synteny between Be-62 and different T. cruzi lineages. It has been suggested that T. cruzi diversity is driven by the evolution of multigene families encoding target antigens of anti-parasite immune responses, located in disruptive regions of the genome. Most studies of Berenice have been conducted on genomic bulk samples, resulting in a biased analysis that favours the dominant genotype. Single-cell omics technologies enable us to study the genetic diversity within an infection caused by protozoan parasites in detail. Sequencing individual genomes of Berenice strains will be the key to elucidating the population structure of individual infections, the dynamics of parasite populations, and adaptive mechanisms.