Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion

Detalhes bibliográficos
Autor(a) principal: Ferreira Rodrigues, Joao Paulo [UNIFESP]
Data de Publicação: 2017
Outros Autores: Takahashi Sant'ana, Guilherme Hideki [UNIFESP], Juliano, Maria Aparecida [UNIFESP], Yoshida, Nobuko [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1128/IAI.00302-17
http://repositorio.unifesp.br/handle/11600/51269
Resumo: Successful infection by Trypanosoma cruzi, the agent of Chagas' disease, is critically dependent on host cell invasion by metacyclic trypomastigote (MT) forms. Two main metacyclic stage-specific surface molecules, gp82 and gp90, play determinant roles in target cell invasion in vitro and in oral T. cruzi infection in mice. The structure and properties of gp82, which is highly conserved among T. cruzi strains, are well known. Information on gp90 is still rather sparse. Here, we attempted to fill that gap. gp90, purified from poorly invasive G strain MT and expressing gp90 at high levels, inhibited HeLa cell lysosome spreading and the gp82mediated internalization of a highly invasive CL strain MT expressing low levels of a diverse gp90 molecule. A recombinant protein containing the conserved C-terminal domain of gp90 exhibited the same properties as the native G strain gp90: it counteracted the host cell lysosome spreading induced by recombinant gp82 and exhibited an inhibitory effect on HeLa cell invasion by CL strain MT. Assays to identify the gp90 sequence associated with the property of downregulating MT invasion, using synthetic peptides spanning the gp90 C-terminal domain, revealed the sequence GVLYTADKEW. These data, plus the findings that lysosome spreading was induced upon HeLa cell interaction with CL strain MT, but not with G strain MT, and that in mixed infection CL strain MT internalization was inhibited by G strain MT, suggest that the inhibition of target cell lysosome spreading is the mechanism by which the gp90 molecule exerts its downregulatory role.
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spelling Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite InvasionTrypanosoma cruzihost cell invasionSuccessful infection by Trypanosoma cruzi, the agent of Chagas' disease, is critically dependent on host cell invasion by metacyclic trypomastigote (MT) forms. Two main metacyclic stage-specific surface molecules, gp82 and gp90, play determinant roles in target cell invasion in vitro and in oral T. cruzi infection in mice. The structure and properties of gp82, which is highly conserved among T. cruzi strains, are well known. Information on gp90 is still rather sparse. Here, we attempted to fill that gap. gp90, purified from poorly invasive G strain MT and expressing gp90 at high levels, inhibited HeLa cell lysosome spreading and the gp82mediated internalization of a highly invasive CL strain MT expressing low levels of a diverse gp90 molecule. A recombinant protein containing the conserved C-terminal domain of gp90 exhibited the same properties as the native G strain gp90: it counteracted the host cell lysosome spreading induced by recombinant gp82 and exhibited an inhibitory effect on HeLa cell invasion by CL strain MT. Assays to identify the gp90 sequence associated with the property of downregulating MT invasion, using synthetic peptides spanning the gp90 C-terminal domain, revealed the sequence GVLYTADKEW. These data, plus the findings that lysosome spreading was induced upon HeLa cell interaction with CL strain MT, but not with G strain MT, and that in mixed infection CL strain MT internalization was inhibited by G strain MT, suggest that the inhibition of target cell lysosome spreading is the mechanism by which the gp90 molecule exerts its downregulatory role.Univ Fed São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Biofis, Escola Paulista Med, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Biofis, Escola Paulista Med, São Paulo, SP, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP: 11/51475-3CNPq: 303825/2015-4Amer Soc Microbiology2019-08-19T11:48:30Z2019-08-19T11:48:30Z2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-http://dx.doi.org/10.1128/IAI.00302-17Infection And Immunity. Washington, v. 85, n. 9, p. -, 2017.10.1128/IAI.00302-170019-9567http://repositorio.unifesp.br/handle/11600/51269WOS:000412696300027enginfo:eu-repo/semantics/openAccessFerreira Rodrigues, Joao Paulo [UNIFESP]Takahashi Sant'ana, Guilherme Hideki [UNIFESP]Juliano, Maria Aparecida [UNIFESP]Yoshida, Nobuko [UNIFESP]reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2021-09-29T11:28:08Zoai:repositorio.unifesp.br/:11600/51269Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652021-09-29T11:28:08Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
title Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
spellingShingle Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
Ferreira Rodrigues, Joao Paulo [UNIFESP]
Trypanosoma cruzi
host cell invasion
title_short Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
title_full Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
title_fullStr Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
title_full_unstemmed Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
title_sort Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
author Ferreira Rodrigues, Joao Paulo [UNIFESP]
author_facet Ferreira Rodrigues, Joao Paulo [UNIFESP]
Takahashi Sant'ana, Guilherme Hideki [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Yoshida, Nobuko [UNIFESP]
author_role author
author2 Takahashi Sant'ana, Guilherme Hideki [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Yoshida, Nobuko [UNIFESP]
author2_role author
author
author
dc.contributor.author.fl_str_mv Ferreira Rodrigues, Joao Paulo [UNIFESP]
Takahashi Sant'ana, Guilherme Hideki [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Yoshida, Nobuko [UNIFESP]
dc.subject.por.fl_str_mv Trypanosoma cruzi
host cell invasion
topic Trypanosoma cruzi
host cell invasion
description Successful infection by Trypanosoma cruzi, the agent of Chagas' disease, is critically dependent on host cell invasion by metacyclic trypomastigote (MT) forms. Two main metacyclic stage-specific surface molecules, gp82 and gp90, play determinant roles in target cell invasion in vitro and in oral T. cruzi infection in mice. The structure and properties of gp82, which is highly conserved among T. cruzi strains, are well known. Information on gp90 is still rather sparse. Here, we attempted to fill that gap. gp90, purified from poorly invasive G strain MT and expressing gp90 at high levels, inhibited HeLa cell lysosome spreading and the gp82mediated internalization of a highly invasive CL strain MT expressing low levels of a diverse gp90 molecule. A recombinant protein containing the conserved C-terminal domain of gp90 exhibited the same properties as the native G strain gp90: it counteracted the host cell lysosome spreading induced by recombinant gp82 and exhibited an inhibitory effect on HeLa cell invasion by CL strain MT. Assays to identify the gp90 sequence associated with the property of downregulating MT invasion, using synthetic peptides spanning the gp90 C-terminal domain, revealed the sequence GVLYTADKEW. These data, plus the findings that lysosome spreading was induced upon HeLa cell interaction with CL strain MT, but not with G strain MT, and that in mixed infection CL strain MT internalization was inhibited by G strain MT, suggest that the inhibition of target cell lysosome spreading is the mechanism by which the gp90 molecule exerts its downregulatory role.
publishDate 2017
dc.date.none.fl_str_mv 2017
2019-08-19T11:48:30Z
2019-08-19T11:48:30Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1128/IAI.00302-17
Infection And Immunity. Washington, v. 85, n. 9, p. -, 2017.
10.1128/IAI.00302-17
0019-9567
http://repositorio.unifesp.br/handle/11600/51269
WOS:000412696300027
url http://dx.doi.org/10.1128/IAI.00302-17
http://repositorio.unifesp.br/handle/11600/51269
identifier_str_mv Infection And Immunity. Washington, v. 85, n. 9, p. -, 2017.
10.1128/IAI.00302-17
0019-9567
WOS:000412696300027
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv -
dc.publisher.none.fl_str_mv Amer Soc Microbiology
publisher.none.fl_str_mv Amer Soc Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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