Differential Infectivity by the Oral Route of Trypanosoma cruzi Lineages Derived from Y Strain

Abstract

BackgroundDiversity of T. cruzi strains is a central problem in Chagas disease research because of its correlation with the wide range of clinical manifestations and the biogeographical parasite distribution. The role played by parasite microdiversity in Chagas disease epidemiology is still debatable. Also awaits clarification whether such diversity is associated with the outcome of oral T. cruzi infection, responsible for frequent outbreaks of acute Chagas disease.Methods and FindingsWe addressed the impact of microdiversity in oral T. cruzi infection, by comparative analysis of two strains, Y30 and Y82, both derived from Y strain, a widely used experimental model. Network genealogies of four nuclear genes (SSU rDNA, actin, DHFR-TS, EF1α) revealed that Y30 is closely related to Discrete Typing Unit TcII while Y82 is more closely related to TcVI, a group containing hybrid strains. Nevertheless, excepting one A-G transition at position 1463, Y30 and Y82 SSU rDNAs were identical. Y82 strain, expressing the surface molecule gp82, infected mice orally more efficiently than Y30, which expresses a related gp30 molecule. Both molecules are involved in lysosome exocytosis-dependent host cell invasion, but exhibit differential gastric mucin-binding capacity, a property critical for parasite migration toward the gastric mucosal epithelium. Upon oral infection of mice, the number of Y30 and Y82 parasites in gastric epithelial cells differed widely.ConclusionsWe conclude that metacyclic forms of gp82-expressing Y82 strain, closely related to TcVI, are better adapted than Y30 strain (TcII) to traverse the stomach mucous layer and establish oral route infection. The efficiency to infect target cell is the same because gp82 and gp30 strains have similar invasion-promoting properties. Unknown is whether differences in Y30 and Y82 are natural parasite adaptations or a product of lab-induced evolution by differential selection along the 60 years elapsed since the Y strain isolation.

Molecular Characterization of Trypanosoma cruzi SAP Proteins with Host-Cell Lysosome Exocytosis-Inducing Activity Required for Parasite Invasion

“…Using immunofluorescence microscopy with a monoclonal antibody to the ubiquitous lysosomal protein Lamp-2, we ascertained that lysosomes were mobilized to the cell periphery upon interaction with SAP-CE, but not with GST (Figure 5D). Lysosome distribution, similar to that induced by recombinant SAP-CE has been observed upon incubation of HeLa cells with recombinant proteins based on molecules implicated in promoting metacyclic trypomastigote internalization, such as GP30 and GP82 [47], [48]. Addition of SAP-CE protein did not result in marked pH change that could influence the lysosome mobilization.…”

Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion

“…Experiments with metacyclic forms of T. cruzi strain Y82, which also engage gp82 to invade host cells (45), revealed that FN inhibits parasite entry into host cells when present at concentrations higher than the cruzipain activity can fully digest, and that treatment of target cells with the recombinant cruzipain increases parasite internalization, whereas the cysteine proteinase inhibitor has the opposite effect (data not shown). Unlike CL and Y82 strains, G strain metacyclic forms, which are less invasive toward human epithelial cells, lacked cruzipain activity.…”

The gp82 Surface Molecule of Trypanosoma cruzi Metacyclic Forms

“…cruzi strains that do not express gp82 on the surface have reduced gastric mucin-binding capacity and, as compared to gp82-expressing MT, they migrate less effi ciently through the gastric mucin-coated transwell fi lter and are poorly infective in mice by the oral route (Cortez et al 2003(Cortez et al , 2012b. Gp82 is engaged by MT of highly infective T .…”