Cruzipain promotes Trypanosoma cruzi adhesion to Rhodnius prolixus midgut.

<h4>Background</h4>Trypanosoma cruzi is the etiological agent of Chagas' disease. Cysteine peptidases are relevant to several aspects of the T. cruzi life cycle and are implicated in parasite-mammalian host relationships. However, little is known about the factors that contribute to...

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Main Authors: Lívia Almeida Uehara, Otacílio C Moreira, Ana Carolina Oliveira, Patrícia Azambuja, Ana Paula Cabral Araujo Lima, Constança Britto, André Luis Souza dos Santos, Marta Helena Branquinha, Claudia Masini d'Avila-Levy
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001958&type=printable
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Summary:<h4>Background</h4>Trypanosoma cruzi is the etiological agent of Chagas' disease. Cysteine peptidases are relevant to several aspects of the T. cruzi life cycle and are implicated in parasite-mammalian host relationships. However, little is known about the factors that contribute to the parasite-insect host interaction.<h4>Methodology/principal findings</h4>Here, we have investigated whether cruzipain could be involved in the interaction of T. cruzi with the invertebrate host. We analyzed the effect of treatment of T. cruzi epimastigotes with anti-cruzipain antibodies or with a panel of cysteine peptidase inhibitors (cystatin, antipain, E-64, leupeptin, iodocetamide or CA-074-OMe) on parasite adhesion to Rhodnius prolixus posterior midgut ex vivo. All treatments, with the exception of CA074-OMe, significantly decreased parasite adhesion to R. prolixus midgut. Cystatin presented a dose-dependent reduction on the adhesion. Comparison of the adhesion rate among several T. cruzi isolates revealed that the G isolate, which naturally possesses low levels of active cruzipain, adhered to a lesser extent in comparison to Dm28c, Y and CL Brener isolates. Transgenic epimastigotes overexpressing an endogenous cruzipain inhibitor (pCHAG), chagasin, and that have reduced levels of active cruzipain adhered to the insect gut 73% less than the wild-type parasites. The adhesion of pCHAG parasites was partially restored by the addition of exogenous cruzipain. In vivo colonization experiments revealed low levels of pCHAG parasites in comparison to wild-type. Parasites isolated after passage in the insect presented a drastic enhancement in the expression of surface cruzipain.<h4>Conclusions/significance</h4>These data highlight, for the first time, that cruzipain contributes to the interaction of T. cruzi with the insect host.
ISSN:1935-2727
1935-2735