ArticleThe Lancet. Microbe2026
Genomic diversity of Trypanosoma cruzi clinical isolates: a retrospective analysis.
Article in The Lancet. Microbe, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTrypanosoma cruzi causes Chagas disease, a poorly understood and clinically heterogeneous disease. Recent work has shown that parasites adapted to laboratory conditions exhibit genomic variation; however, little is known of the extent of genomic diversity among clinically isolated specimens. In this study, we aimed to describe genomic diversity within a set of clinically isolated strains.
methodsWe isolated 15 T cruzi specimens from three cross-sectional clinical studies of Chagas disease in Bolivia. We sequenced the genome of each strain, estimated parasite genetic lineage, genomic population structure, and regions of copy number plasticity, and identified gene conversion events. We generated and annotated genome assemblies of each isolate and compared the gene repertoires encoding the multigene families (MGFs) of T cruzi.
findingsWe identified parasites from two genetic lineages in this collection of clinical isolates. Our analysis revealed evidence of genomic instability, copy number variation, and regions with loss of heterozygosity. We also discovered a set of MGF members present in all the clinically isolated parasite genomes and absent from all the laboratory-adapted strains assessed in our comparative dataset, regardless of parasite lineage. MGF repertoires from genomes of the same lineage were more conserved in content among field-isolated specimens than among culture-adapted strains.
interpretationThis study provides, to the best of our knowledge, the first whole-genome sequencing data for TcV parasites isolated from human participants with Chagas disease. Our analysis of these genomes revealed genomic instability; moreover, we observed a set of genes that are present exclusively within clinical isolates and absent in laboratory-adapted strains, indicating evolutionary pressure for the maintenance of these genes in natural hosts. These findings highlight the limitations of genetic studies focused exclusively on laboratory-adapted parasite strains, which could miss genomic features of T cruzi that might be important for clinical infection.
fundingNIH Global Research Training Grant, NIAD grant, Johns Hopkins University Discovery Award, the Biotechnology and Biological Sciences Research Council Doctoral Training Grant, The Dr Gordon Smith Travelling Fellowship, The Chadwick Trust Travelling Scholarship, and Royal Society of Tropical Medicine and Hygiene grant.
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