Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation

ABSTRACT Enteropathogenic Escherichia coli and enterohemorrhagic E. coli (EPEC and EHEC, respectively) are extracellular pathogens that reorganize the host cell cytoskeleton to form “actin pedestals” beneath the tightly adherent bacteria, a critical step in pathogenesis. EPEC and EHEC inject effecto...

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Autores principales:	Vikash Singh, Anthony Davidson, Peter J. Hume, Vassilis Koronakis
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	actin EPEC EspG GTPases p21-activated kinases Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/881b0ecdafa640f1b338d8fe887cc529
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spelling	oai:doaj.org-article:881b0ecdafa640f1b338d8fe887cc5292021-11-15T16:22:10ZPathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation10.1128/mBio.01876-192150-7511https://doaj.org/article/881b0ecdafa640f1b338d8fe887cc5292019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01876-19https://doaj.org/toc/2150-7511ABSTRACT Enteropathogenic Escherichia coli and enterohemorrhagic E. coli (EPEC and EHEC, respectively) are extracellular pathogens that reorganize the host cell cytoskeleton to form “actin pedestals” beneath the tightly adherent bacteria, a critical step in pathogenesis. EPEC and EHEC inject effector proteins that manipulate host cell signaling cascades to trigger pedestal assembly. One such effector, EspG, has been reported to bind and activate p21-activated kinase (PAK), a key cytoskeletal regulator, but the function of this interaction and whether it impacts pedestal assembly are unknown. Here, we demonstrate that deletion of espG significantly impairs pedestal formation and attachment by both EPEC and EHEC. This role of EspG is shown to be dependent on its interaction with PAK. Unexpectedly, EspG was able to subvert PAK only in the presence of Rho family small GTPases, which function to both concentrate PAK at the membrane and stimulate PAK activation. Our findings reveal a novel mechanism by which EspG hijacks PAK and sustains its active state to drive bacterial attachment to host cells. IMPORTANCE Enteropathogenic E. coli and enterohemorrhagic E. coli (EPEC and EHEC, respectively) remain a significant global health problem. Both EPEC and EHEC initiate infection by attaching to cells in the host intestine, triggering the formation of actin-rich “pedestal” structures directly beneath the adherent pathogen. These bacteria inject their own receptor into host cells, which upon binding to a protein on the pathogen surface triggers pedestal formation. Multiple other proteins are also delivered into the cells of the host intestine, but how they contribute to disease is often less clear. Here, we show how one of these injected proteins, EspG, hijacks a host signaling pathway for pedestal production. This provides new insights into this essential early stage in EPEC and EHEC disease.Vikash SinghAnthony DavidsonPeter J. HumeVassilis KoronakisAmerican Society for MicrobiologyarticleactinEPECEspGGTPasesp21-activated kinasesMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	actin EPEC EspG GTPases p21-activated kinases Microbiology QR1-502
spellingShingle	actin EPEC EspG GTPases p21-activated kinases Microbiology QR1-502 Vikash Singh Anthony Davidson Peter J. Hume Vassilis Koronakis Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation
description	ABSTRACT Enteropathogenic Escherichia coli and enterohemorrhagic E. coli (EPEC and EHEC, respectively) are extracellular pathogens that reorganize the host cell cytoskeleton to form “actin pedestals” beneath the tightly adherent bacteria, a critical step in pathogenesis. EPEC and EHEC inject effector proteins that manipulate host cell signaling cascades to trigger pedestal assembly. One such effector, EspG, has been reported to bind and activate p21-activated kinase (PAK), a key cytoskeletal regulator, but the function of this interaction and whether it impacts pedestal assembly are unknown. Here, we demonstrate that deletion of espG significantly impairs pedestal formation and attachment by both EPEC and EHEC. This role of EspG is shown to be dependent on its interaction with PAK. Unexpectedly, EspG was able to subvert PAK only in the presence of Rho family small GTPases, which function to both concentrate PAK at the membrane and stimulate PAK activation. Our findings reveal a novel mechanism by which EspG hijacks PAK and sustains its active state to drive bacterial attachment to host cells. IMPORTANCE Enteropathogenic E. coli and enterohemorrhagic E. coli (EPEC and EHEC, respectively) remain a significant global health problem. Both EPEC and EHEC initiate infection by attaching to cells in the host intestine, triggering the formation of actin-rich “pedestal” structures directly beneath the adherent pathogen. These bacteria inject their own receptor into host cells, which upon binding to a protein on the pathogen surface triggers pedestal formation. Multiple other proteins are also delivered into the cells of the host intestine, but how they contribute to disease is often less clear. Here, we show how one of these injected proteins, EspG, hijacks a host signaling pathway for pedestal production. This provides new insights into this essential early stage in EPEC and EHEC disease.
format	article
author	Vikash Singh Anthony Davidson Peter J. Hume Vassilis Koronakis
author_facet	Vikash Singh Anthony Davidson Peter J. Hume Vassilis Koronakis
author_sort	Vikash Singh
title	Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation
title_short	Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation
title_full	Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation
title_fullStr	Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation
title_full_unstemmed	Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation
title_sort	pathogenic <named-content content-type="genus-species">escherichia coli</named-content> hijacks gtpase-activated p21-activated kinase for actin pedestal formation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/881b0ecdafa640f1b338d8fe887cc529
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_version_	1718426913468317696

Pathogenic <named-content content-type="genus-species">Escherichia coli</named-content> Hijacks GTPase-Activated p21-Activated Kinase for Actin Pedestal Formation

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