Role of GP82 in the Selective Binding to Gastric Mucin during Oral Infection with Trypanosoma cruzi

Role of GP82 in the Selective Binding to Gastric Mucin during Oral Infection with Trypanosoma cruzi

Author Staquicini, Daniela I. Autor UNIFESP Google Scholar
Martins, Rafael M. Autor UNIFESP Google Scholar
Macedo, Silene Autor UNIFESP Google Scholar
Sasso, Gisela R. S. Autor UNIFESP Google Scholar
Atayde, Vanessa Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Yoshida, Nobuko Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Yale Univ
Abstract Oral infection by Trypanosoma cruzi has been the primary cause of recent outbreaks of acute Chagas' diseases. This route of infection may involve selective binding of the metacyclic trypomastigote surface molecule gp82 to gastric mucin as a first step towards invasion of the gastric mucosal epithelium and subsequent systemic infection. Here we addressed that question by performing in vitro and in vivo experiments. A recombinant protein containing the complete gp82 sequence (J18), a construct lacking the gp82 central domain (J18*), and 20-mer synthetic peptides based on the gp82 central domain, were used for gastric mucin binding and HeLa cell invasion assays, or for in vivo experiments. Metacyclic trypomastigotes and J18 bound to gastric mucin whereas J18* failed to bind. Parasite or J18 binding to submaxillary mucin was negligible. HeLa cell invasion by metacyclic forms was not affected by gastric mucin but was inhibited in the presence of submaxillary mucin. of peptides tested for inhibition of J18 binding to gastric mucin, the inhibitory peptide p7 markedly reduced parasite invasion of HeLa cells in the presence of gastric mucin. Peptide p7*, with the same composition as p7 but with a scrambled sequence, had no effect. Mice fed with peptide p7 before oral infection with metacyclic forms developed lower parasitemias than mice fed with peptide p7*. Our results indicate that selective binding of gp82 to gastric mucin may direct T. cruzi metacyclic trypomastigotes to stomach mucosal epithelium in oral infection.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2006/61450-0
CNPq: 470726/2007-5
Date 2010-03-01
Published in Plos Neglected Tropical Diseases. San Francisco: Public Library Science, v. 4, n. 3, 9 p., 2010.
ISSN 1935-2727 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 9
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000276312200029

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