Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , |
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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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 |
_version_ |
1814268377849397248 |