Characterization of the infective properties of a new genetic group of Trypanosoma cruzi associated with bats

Abstract

A new genotype of Trypanosoma cruzi, associated with bats from anthropic areas, was recently described. Here we characterized a T. cruzi strain from this new genetic group, which could be a potential source of infection to humans. Metacyclic trypomastigotes (MT) of this strain, herein designated BAT, were compared to MT of well characterized CL and G strains, as regards the surface profile and infectivity toward human epithelial HeLa cells. BAT strain MT expressed gp82, the surface molecule recognized by monoclonal antibody 3F6 and known to promote CL strain invasion by inducing lysosomal exocytosis, as well as mucin-like molecules, but lacked gp90, which functions as a negative regulator of invasion in G strain. A set of experiments indicated that BAT strain internalization is gp82-mediated, and requires the activation of host cell phosphatidylinositol 3-kinase, protein kinase C and the mammalian target of rapamycin. MT of BAT strain were able to migrate through a gastric mucin layer, a property associated with p82 and relevant for oral infection. Gp82 was found to be a highly conserved molecule. Analysis of the BAT strain gp82 domain, containing the cell binding- and gastric mucin-binding sites, showed 91 and 93% sequence identity with G and CL strains, respectively. Hela cell invasion by BAT strain MT was inhibited by purified mucin-like molecules, which were shown to affect lysosome exocytosis required for MT internalization. Although MT of BAT strain infected host cells in vitro, they were less effective than G or CL strains in infecting mice either orally or intraperitoneally.

Ecological scenario and Trypanosoma cruzi DTU characterization of a fatal acute Chagas disease case transmitted orally (Espírito Santo state, Brazil)

“…This species, which is closely related to T. cruzi , is able to invade mammalian cells as previously demonstrated experimentally [95, 96] and to form cysts in cardiac tissue [97]. We detected T. dionisii directly from cardiac tissue more than two weeks after the infection of the patient.…”

The gp82 Surface Molecule of Trypanosoma cruzi Metacyclic Forms

“…6.1 ). The amino acid substitutions found in BAT strain sequences P4, P7 and P8, are mostly conservative and apparently do not affect the gp82 function (Maeda et al 2011 ). On the other hand, consistent with the sequence/function relationship, a gp82 family member C03 that displays considerable differences in P4 and P8 sequences (Fig.…”

“…MT binding to target cells mediated by gp35/50 triggers the activation of signaling pathways distinct from those induced by gp82 (Neira et al 2002 ;Ferreira et al 2006 ). Rather than promoting the lysosome exocytosis, gp35/50 binding to HeLa cells impaired lysosome mobilization (Maeda et al 2011 ). The properties of gp35/50 molecules, quite distinct from gp82, have contributed to further reinforce the role played by gp82 in MT invasion of host cells.…”

“…Gp82 is highly conserved among genetically divergent T . cruzi strains, such as G, CL and BAT, which share >90 % sequence identity (Maeda et al 2011 ). These strains, originated from different sources in distant geographical regions, have been used to study the multiple aspects of parasitism.…”

Bats as Potential Reservoir Hosts for Vector-Borne Diseases

“…Maeda et al 2011;Marcili et al 2009) and the strong association between bats and, for instance, Schizotryphanum suggests a long shared evolutionary development (García et al 2012). Furthermore, the molecular examination of Chagas virus strains reveals the movement of bats, naturally or by human transport, between the Old and the New World (Hamilton et al 2012b).…”