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- Title
Trypanosoma cruzi TcSMUG L-surface Mucins Promote Development and Infectivity in the Triatomine Vector Rhodnius prolixus.
- Authors
Gonzalez, Marcelo S.; Souza, Marcela S.; Garcia, Eloi S.; Nogueira, Nadir F. S.; Mello, Cícero B.; Cánepa, Gaspar E.; Bertotti, Santiago; Durante, Ignacio M.; Azambuja, Patrícia; Buscaglia, Carlos A.
- Abstract
Background: TcSMUG L products were recently identified as novel mucin-type glycoconjugates restricted to the surface of insect-dwelling epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas disease. The remarkable conservation of their predicted mature N-terminal region, which is exposed to the extracellular milieu, suggests that TcSMUG L products may be involved in structural and/or functional aspects of the interaction with the insect vector. Methodology and Principal Findings: Here, we investigated the putative roles of TcSMUG L mucins in both in vivo development and ex vivo attachment of epimastigotes to the luminal surface of the digestive tract of Rhodnius prolixus. Our results indicate that the exogenous addition of TcSMUG L N-terminal peptide, but not control T. cruzi mucin peptides, to the infected bloodmeal inhibited the development of parasites in R. prolixus in a dose-dependent manner. Pre-incubation of insect midguts with the TcSMUG L peptide impaired the ex vivo attachment of epimastigotes to the luminal surface epithelium, likely by competing out TcSMUG L binding sites on the luminal surface of the posterior midgut, as revealed by fluorescence microscopy. Conclusion and Significance: Together, these observations indicate that TcSMUG L mucins are a determinant of both adhesion of T. cruzi epimastigotes to the posterior midgut epithelial cells of the triatomine, and the infection of the insect vector, R. prolixus. Author Summary: Chagas disease, the major tropical human disease in much of Latin America, affects approximately 11 million people. There are 300,000 new cases of Chagas disease and approximately 21,000 deaths, annually. Triatomine vectors, including Rhodnius prolixus, are able to transmit the protozoan Trypanosoma cruzi, the etiological agent of disease. To develop within insects, the flagellates undergo morphological changes, modulating surface molecules to enable interactions with insect tissues such as the perimicrovilar membranes in the midgut which is an essential step for their development and successful transmission to a vertebrate host. The surface of T. cruzi is covered in glycosyl phosphatidylinositol (GPI)-anchored mucin molecules that determine parasite protection and establishment of a persistent infection in vertebrates. A particular kind of mucin, termed TcSMUG L, is only present at surface of the insect-dwelling stages of protozoan and, according to our results, it is involved in the interaction between T. cruzi and its invertebrate host, determining both the ex vivo adhesion to the insect midgut cells and the in vivo development in the vector. Collectively, our work adds new insight into the relevance of mucin-type glycoconjugates in the infection of insect vectors and points to them as promising targets to develop transmission-blocking strategies for this disease.
- Subjects
RHODNIUS prolixus; TRYPANOSOMA cruzi; MUCINS; CHAGAS' disease; PEPTIDES; MUCINOUS adenocarcinoma
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 11, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002552