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Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation

Shigella invasion and dissemination in intestinal epithelial cells relies on a type 3 secretion system (T3SS), which mediates translocation of virulence proteins into host cells. T3SSs are composed of three major parts: an extracellular needle, a basal body, and a cytoplasmic complex. Three categori...

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Autores principales: Kadari, Mahendar, Lakhloufi, Dalila, Delforge, Valérie, Imbault, Virginie, Communi, David, Smeesters, Pierre, Botteaux, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925163/
https://www.ncbi.nlm.nih.gov/pubmed/31517452
http://dx.doi.org/10.1002/mbo3.932
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author Kadari, Mahendar
Lakhloufi, Dalila
Delforge, Valérie
Imbault, Virginie
Communi, David
Smeesters, Pierre
Botteaux, Anne
author_facet Kadari, Mahendar
Lakhloufi, Dalila
Delforge, Valérie
Imbault, Virginie
Communi, David
Smeesters, Pierre
Botteaux, Anne
author_sort Kadari, Mahendar
collection PubMed
description Shigella invasion and dissemination in intestinal epithelial cells relies on a type 3 secretion system (T3SS), which mediates translocation of virulence proteins into host cells. T3SSs are composed of three major parts: an extracellular needle, a basal body, and a cytoplasmic complex. Three categories of proteins are hierarchically secreted: (a) the needle components, (b) the translocator proteins which form a pore (translocon) inside the host cell membrane and (c) the effectors interfering with the host cell signaling pathways. In the absence of host cell contact, the T3SS is maintained in an “off” state by the presence of a tip complex. Secretion is activated by host cell contact which allows the release of a gatekeeper protein called MxiC. In this work, we have investigated the role of Spa33, a component of the cytoplasmic complex, in the regulation of secretion. The spa33 gene encodes a 33‐kDa protein and a smaller fragment of 12 kDa (Spa33(C)) which are both essential components of the cytoplasmic complex. We have shown that the spa33 gene gives rise to 5 fragments of various sizes. Among them, three are necessary for T3SS. Interestingly, we have shown that Spa33 is implicated in the regulation of secretion. Indeed, the mutation of a single residue in Spa33 induces an effector mutant phenotype, in which MxiC is sequestered. Moreover, we have shown a direct interaction between Spa33 and MxiC.
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spelling pubmed-69251632019-12-24 Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation Kadari, Mahendar Lakhloufi, Dalila Delforge, Valérie Imbault, Virginie Communi, David Smeesters, Pierre Botteaux, Anne Microbiologyopen Original Articles Shigella invasion and dissemination in intestinal epithelial cells relies on a type 3 secretion system (T3SS), which mediates translocation of virulence proteins into host cells. T3SSs are composed of three major parts: an extracellular needle, a basal body, and a cytoplasmic complex. Three categories of proteins are hierarchically secreted: (a) the needle components, (b) the translocator proteins which form a pore (translocon) inside the host cell membrane and (c) the effectors interfering with the host cell signaling pathways. In the absence of host cell contact, the T3SS is maintained in an “off” state by the presence of a tip complex. Secretion is activated by host cell contact which allows the release of a gatekeeper protein called MxiC. In this work, we have investigated the role of Spa33, a component of the cytoplasmic complex, in the regulation of secretion. The spa33 gene encodes a 33‐kDa protein and a smaller fragment of 12 kDa (Spa33(C)) which are both essential components of the cytoplasmic complex. We have shown that the spa33 gene gives rise to 5 fragments of various sizes. Among them, three are necessary for T3SS. Interestingly, we have shown that Spa33 is implicated in the regulation of secretion. Indeed, the mutation of a single residue in Spa33 induces an effector mutant phenotype, in which MxiC is sequestered. Moreover, we have shown a direct interaction between Spa33 and MxiC. John Wiley and Sons Inc. 2019-09-13 /pmc/articles/PMC6925163/ /pubmed/31517452 http://dx.doi.org/10.1002/mbo3.932 Text en © 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Kadari, Mahendar
Lakhloufi, Dalila
Delforge, Valérie
Imbault, Virginie
Communi, David
Smeesters, Pierre
Botteaux, Anne
Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation
title Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation
title_full Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation
title_fullStr Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation
title_full_unstemmed Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation
title_short Multiple proteins arising from a single gene: The role of the Spa33 variants in Shigella T3SS regulation
title_sort multiple proteins arising from a single gene: the role of the spa33 variants in shigella t3ss regulation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925163/
https://www.ncbi.nlm.nih.gov/pubmed/31517452
http://dx.doi.org/10.1002/mbo3.932
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