Article
MDL28170, a calpain inhibitor, affects Trypanosoma cruzi metacyclogenesis, ultrastructure and attachment to Rhodnius prolixus midgut
Registration in:
VIDAL, Vitor Ennes; et al. MDL28170, a Calpain Inhibitor, Affects Trypanosoma cruzi Metacyclogenesis, Ultrastructure and Attachment to Rhodnius prolixus Midgut. Plos One, v.6, n.4, e18371, 9p, Apr. 2011.
1932-6203
10.1371/journal.pone.0018371
Author
Vidal, Vítor Ennes
Menna-Barreto, Rubem F. S.
Santos, André L. S.
Branquinha, Marta H.
d`Avila-Levy, Claudia M.
Abstract
Background: Trypanosoma cruzi is the etiological agent of Chagas’ disease. During the parasite life cycle, many molecules
are involved in the differentiation process and infectivity. Peptidases are relevant for crucial steps of T. cruzi life cycle; as
such, it is conceivable that they may participate in the metacyclogenesis and interaction with the invertebrate host.
Methodology/Principal Findings: In this paper, we have investigated the effect of the calpain inhibitor MDL28170 on the
attachment of T. cruzi epimastigotes to the luminal midgut surface of Rhodnius prolixus, as well as on the metacyclogenesis
process and ultrastructure. MDL28170 treatment was capable of significantly reducing the number of bound epimastigotes
to the luminal surface midgut of the insect. Once the cross-reactivity of the anti-Dm-calpain was assessed, it was possible to
block calpain molecules by the antibody, leading to a significant reduction in the capacity of adhesion to the insect guts by
T. cruzi. However, the antibodies were unable to interfere in metacyclogenesis, which was impaired by the calpain inhibitor
presenting a significant reduction in the number of metacyclic trypomastigotes. The calpain inhibitor also promoted a direct
effect against bloodstream trypomastigotes. Ultrastructural analysis of epimastigotes treated with the calpain inhibitor
revealed disorganization in the reservosomes, Golgi and plasma membrane disruption.
Conclusions/Significance: The presence of calpain and calpain-like molecules in a wide range of organisms suggests that
these proteins could be necessary for basic cellular functions. Herein, we demonstrated the effects of MDL28170 in crucial
steps of the T. cruzi life cycle, such as attachment to the insect midgut and metacyclogenesis, as well as in parasite viability
and morphology. Together with our previous findings, these results help to shed some light on the functions of T. cruzi
calpains. Considering the potential roles of these molecules on the interaction with both invertebrate and vertebrate hosts,
it is interesting to improve knowledge on these molecules in T. cruzi.