Motility of trypomastigotes and virulence in Trypanosoma

COSENZA, M; MASIP, Y; TEKIEL V

CABA

Simposio; Frontiers in Bioscience 4 Symposium; 2023

IBIOBA

Abstract for Frontiers in Bioscience 4 Symposium13-15 sept 2023, Buenos AiresMotility of trypomastigotes and virulence in Trypanosoma cruziCosenza M, Masip YE, Tekiel V.Trypanosoma cruzi is the flagellated parasite that causes Chagas’ disease, currently infecting 6-7 million people worldwide. The mechanism by which T. cruzi disseminates to several organs during the early acute infection is not completely understood. However, this process is mediated by bloodstream trypomastigotes, whose tissue tropism and intratissular migration ability will impact later in the development of the chronic disease. Previously, we have shown that trypomastigotes of different T. cruzi strains differ in their ability to transmigrate into three-dimensional cultured spheroids: high virulent strains (i.e. RA) deepen up to 50µm, while low virulent strains (i.e. Acosta or K98) remained at the spheroid surface (Rodríguez et al., 2020). As transmigration has been linked to pathogen motility in other microorganisms, we investigated the motility patterns of trypomastigotes in three-dimensional collagen I matrixes. Approximately 900 trypomastigotes acquired by time-lapse microscopy (2 images/sec for 1 min) were tracked, analyzed with ImageJ/Plugin/ManualTracking software, and classified as: persistent (rectilinear movement), intermittent (alternate rectilinear movement with change of direction) or tumbler (non-directional movement and no displacement). While 93,3% of trypomastigotes from K98 strain presented tumbler motility, trypomastigotes of the high virulent RA strain were 14% persistent, 35,2% intermittent and 50,9% tumblers. Then, subpopulations of RA strain were isolated by a free-swimming assay; trypomastigotes with higher swimming capacity (fast) were enriched with intermittent (65,5%) and persistent (27,5%) parasites, while those with low swimming capacity (slow) were essentially tumbler parasites (85,2%). Fast and slow subpopulations also differ in their infectivity in vitro and virulence in vivo; mice infected with fast trypomastigotes presented 75% mortality and higher parasitemia. These results strongly suggest a link between trypomastigote motility and virulence. Whether parasite motility is directly implicated in transmigration remains to be determined yet.