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Published on: July 31, 2019
Inactive trans-Sialidase Expression in iTS-null Trypanosoma cruzi Generates Virulent Trypomastigotes
Carla A Pascuale1,2, Juan M Burgos1,2, Miriam Postan2,3
1Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina.
Abstract:
Disclosing virulence factors from pathogens is required to better understand the pathogenic mechanisms involved in their interaction with the host. In the case of Trypanosoma cruzi several molecules are associated with virulence. Among them, the trans-sialidase (TS) has arisen as one of particular relevance due to its effect on the immune system and involvement in the interaction/invasion of the host cells. The presence of conserved genes encoding for an inactive TS (iTS) isoform is puzzlingly restricted to the genome of parasites from the Discrete Typing Units TcII, TcV, and TcVI, which include highly virulent strains. Previous in vitro results using recombinant iTS support that this isoform could play a different or complementary pathogenic role to that of the enzymatically active protein. However, direct evidence involving iTS in in vivo pathogenesis and invasion is still lacking. Here we faced this challenge by transfecting iTS-null parasites with a recombinant gene that allowed us to follow its expression and association with pathological events. We found that iTS expression improves parasite invasion of host cells and increases their in vivo virulence for mice as shown by histopathologic findings in heart and skeletal muscle.
Insights
The inactive trans-sialidase (iTS) of Trypanosoma cruzi enhances parasite invasion and increases virulence in mice. This finding reveals a novel pathogenic role for iTS in Chagas disease.
Area of Science:
- Molecular Parasitology
- Infectious Diseases
- Host-Pathogen Interactions
Background:
- Understanding pathogen virulence factors is crucial for deciphering host-pathogen interactions.
- Trypanosoma cruzi possesses several virulence molecules, including trans-sialidase (TS).
- An inactive TS (iTS) isoform, found in virulent T. cruzi strains, has a poorly understood pathogenic role.
Purpose of the Study:
- To investigate the in vivo role of the inactive trans-sialidase (iTS) in Trypanosoma cruzi pathogenesis and host cell invasion.
- To provide direct evidence for iTS involvement in disease progression and parasite infectivity.
Main Methods:
- Generation of iTS-null Trypanosoma cruzi parasites.
- Transfection of iTS-null parasites with a recombinant iTS gene for expression tracking.
- Assessment of parasite invasion efficiency in host cells.
- Evaluation of in vivo virulence in a mouse model, including histopathological analysis of heart and skeletal muscle.
Main Results:
- Expression of iTS significantly improved Trypanosoma cruzi invasion of host cells.
- iTS expression led to increased parasite virulence in mice.
- Histopathological examination revealed notable changes in heart and skeletal muscle tissues of infected mice.
Conclusions:
- The inactive trans-sialidase (iTS) isoform of Trypanosoma cruzi plays a direct role in enhancing parasite invasion.
- iTS contributes to the overall virulence of Trypanosoma cruzi in vivo, impacting host tissues.
- These findings highlight iTS as a potential target for therapeutic strategies against Chagas disease.
