A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins

ABSTRACT The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly...

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Autores principales:	Farid Tejeda-Dominguez, Jazmin Huerta-Cantillo, Lucia Chavez-Dueñas, Fernando Navarro-Garcia
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	EspA filament EspB-EspD pore EspC protein binding protein translocation secretion systems Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/916bb35c9f444192bd3c7f55365ae57b
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spelling	oai:doaj.org-article:916bb35c9f444192bd3c7f55365ae57b2021-11-15T15:50:59ZA Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins10.1128/mBio.00184-172150-7511https://doaj.org/article/916bb35c9f444192bd3c7f55365ae57b2017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00184-17https://doaj.org/toc/2150-7511ABSTRACT The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic Escherichia coli (EPEC) autotransporter, and YopH, a protein detected on the surface of Yersinia, require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore. Interestingly, this novel mechanism does not exclude the injection model (i.e., EspF) operating through the T3SS conduit; therefore, T3SS can be functioning as an internal conduit or as an external railway, which can be used to reach the translocator pore, and this mechanism appears to be conserved among different T3SS-dependent pathogens. IMPORTANCE The type 3 secretion system is essential for injection of virulence factors, which are delivered directly into the cytosol of the host cells for usurping and subverting host processes. Recent studies have shown that these effectors proteins indeed travel inside an “injectisome” conduit through a single step of translocation by connecting the bacterium and host cell cytoplasms. However, all findings are not compatible with this model. For example, both YopH, a protein detected on the surface of Yersinia, and EspC, an autotransporter protein secreted by enteropathogenic E. coli, require a functional T3SS for host cell translocation. Both proteins have an intermediate extracellular step before their T3SS-dependent translocation. Here, we show an alternative delivery mechanism for these extracellularly secreted virulence factors that are then incorporated into the T3SS to enter the cells; this novel mechanism coexists with but diverges from the canonical injection model that involves the passage of the protein inside the injectisome.Farid Tejeda-DominguezJazmin Huerta-CantilloLucia Chavez-DueñasFernando Navarro-GarciaAmerican Society for MicrobiologyarticleEspA filamentEspB-EspD poreEspCprotein bindingprotein translocationsecretion systemsMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	EspA filament EspB-EspD pore EspC protein binding protein translocation secretion systems Microbiology QR1-502
spellingShingle	EspA filament EspB-EspD pore EspC protein binding protein translocation secretion systems Microbiology QR1-502 Farid Tejeda-Dominguez Jazmin Huerta-Cantillo Lucia Chavez-Dueñas Fernando Navarro-Garcia A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins
description	ABSTRACT The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic Escherichia coli (EPEC) autotransporter, and YopH, a protein detected on the surface of Yersinia, require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore. Interestingly, this novel mechanism does not exclude the injection model (i.e., EspF) operating through the T3SS conduit; therefore, T3SS can be functioning as an internal conduit or as an external railway, which can be used to reach the translocator pore, and this mechanism appears to be conserved among different T3SS-dependent pathogens. IMPORTANCE The type 3 secretion system is essential for injection of virulence factors, which are delivered directly into the cytosol of the host cells for usurping and subverting host processes. Recent studies have shown that these effectors proteins indeed travel inside an “injectisome” conduit through a single step of translocation by connecting the bacterium and host cell cytoplasms. However, all findings are not compatible with this model. For example, both YopH, a protein detected on the surface of Yersinia, and EspC, an autotransporter protein secreted by enteropathogenic E. coli, require a functional T3SS for host cell translocation. Both proteins have an intermediate extracellular step before their T3SS-dependent translocation. Here, we show an alternative delivery mechanism for these extracellularly secreted virulence factors that are then incorporated into the T3SS to enter the cells; this novel mechanism coexists with but diverges from the canonical injection model that involves the passage of the protein inside the injectisome.
format	article
author	Farid Tejeda-Dominguez Jazmin Huerta-Cantillo Lucia Chavez-Dueñas Fernando Navarro-Garcia
author_facet	Farid Tejeda-Dominguez Jazmin Huerta-Cantillo Lucia Chavez-Dueñas Fernando Navarro-Garcia
author_sort	Farid Tejeda-Dominguez
title	A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins
title_short	A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins
title_full	A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins
title_fullStr	A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins
title_full_unstemmed	A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins
title_sort	novel mechanism for protein delivery by the type 3 secretion system for extracellularly secreted proteins
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/916bb35c9f444192bd3c7f55365ae57b
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A Novel Mechanism for Protein Delivery by the Type 3 Secretion System for Extracellularly Secreted Proteins

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