EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways

ABSTRACT The translocation of effectors into the host cell through type 3 secretion systems (T3SS) is a sophisticated strategy employed by pathogenic bacteria to subvert host responses and facilitate colonization. Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) utilize...

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Autores principales:	Fernando H. Martins, Ashwani Kumar, Cecilia M. Abe, Eneas Carvalho, Milton Nishiyama-Jr, Chao Xing, Vanessa Sperandio, Waldir P. Elias
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	enteropathogenic E. coli EspFu/TccP Tir phosphorylation pedestal formation inflammation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/12aa13d049e145149b9e0a0bf7ce0d36
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spelling	oai:doaj.org-article:12aa13d049e145149b9e0a0bf7ce0d362021-11-15T15:57:03ZEspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways10.1128/mBio.00617-202150-7511https://doaj.org/article/12aa13d049e145149b9e0a0bf7ce0d362020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00617-20https://doaj.org/toc/2150-7511ABSTRACT The translocation of effectors into the host cell through type 3 secretion systems (T3SS) is a sophisticated strategy employed by pathogenic bacteria to subvert host responses and facilitate colonization. Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) utilize the Tir and EspFu (also known as TccP) effectors to remodel the host cytoskeleton, culminating in the formation of attaching and effacing (AE) lesions on enterocytes. While some EPEC strains require tyrosine phosphorylation of Tir and recruitment of the host Nck to trigger actin polymerization, EHEC and certain EPEC strains, whose Tir is not phosphorylated, rely on the effector EspFu for efficient actin remodeling. Here, we investigated the role played by Tir-Nck and Tir-EspFu actin polymerization pathways during the infection of epithelial cells, as well as the host transcriptional response to the AE lesion formation induced by EPEC. We found that EspFu-mediated actin assembly promotes bacterial attachment and epithelial colonization more efficiently than Tir-Nck. Moreover, we showed that both actin polymerization mechanisms can activate inflammatory pathways and reverse the anti-inflammatory response induced by EPEC in epithelial cells. However, this activity is remarkably more evident in infections with EspFu-expressing EPEC strains. This study demonstrates the complex interactions between effector-mediated actin remodeling and inflammation. Different strains carry different combinations of these two effectors, highlighting the plasticity of pathogenic E. coli enteric infections. IMPORTANCE EPEC is among the leading causes of diarrheal disease worldwide. The colonization of the gut mucosa by EPEC results in actin pedestal formation at the site of bacterial attachment. These pedestals are referred to as attaching and effacing (AE) lesions. Here, we exploit the different molecular mechanisms used by EPEC to induce AE lesions on epithelial cells, showing that the effector EspFu is associated with increased bacterial attachment and enhanced epithelial colonization compared to the Tir-Nck pathway. Moreover, we also showed that actin pedestal formation can counterbalance the anti-inflammatory activity induced by EPEC, especially when driven by EspFu. Collectively, our findings provide new insights into virulence mechanisms employed by EPEC to colonize epithelial cells, as well as the host response to this enteric pathogen.Fernando H. MartinsAshwani KumarCecilia M. AbeEneas CarvalhoMilton Nishiyama-JrChao XingVanessa SperandioWaldir P. EliasAmerican Society for Microbiologyarticleenteropathogenic E. coliEspFu/TccPTir phosphorylationpedestal formationinflammationMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	enteropathogenic E. coli EspFu/TccP Tir phosphorylation pedestal formation inflammation Microbiology QR1-502
spellingShingle	enteropathogenic E. coli EspFu/TccP Tir phosphorylation pedestal formation inflammation Microbiology QR1-502 Fernando H. Martins Ashwani Kumar Cecilia M. Abe Eneas Carvalho Milton Nishiyama-Jr Chao Xing Vanessa Sperandio Waldir P. Elias EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways
description	ABSTRACT The translocation of effectors into the host cell through type 3 secretion systems (T3SS) is a sophisticated strategy employed by pathogenic bacteria to subvert host responses and facilitate colonization. Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) utilize the Tir and EspFu (also known as TccP) effectors to remodel the host cytoskeleton, culminating in the formation of attaching and effacing (AE) lesions on enterocytes. While some EPEC strains require tyrosine phosphorylation of Tir and recruitment of the host Nck to trigger actin polymerization, EHEC and certain EPEC strains, whose Tir is not phosphorylated, rely on the effector EspFu for efficient actin remodeling. Here, we investigated the role played by Tir-Nck and Tir-EspFu actin polymerization pathways during the infection of epithelial cells, as well as the host transcriptional response to the AE lesion formation induced by EPEC. We found that EspFu-mediated actin assembly promotes bacterial attachment and epithelial colonization more efficiently than Tir-Nck. Moreover, we showed that both actin polymerization mechanisms can activate inflammatory pathways and reverse the anti-inflammatory response induced by EPEC in epithelial cells. However, this activity is remarkably more evident in infections with EspFu-expressing EPEC strains. This study demonstrates the complex interactions between effector-mediated actin remodeling and inflammation. Different strains carry different combinations of these two effectors, highlighting the plasticity of pathogenic E. coli enteric infections. IMPORTANCE EPEC is among the leading causes of diarrheal disease worldwide. The colonization of the gut mucosa by EPEC results in actin pedestal formation at the site of bacterial attachment. These pedestals are referred to as attaching and effacing (AE) lesions. Here, we exploit the different molecular mechanisms used by EPEC to induce AE lesions on epithelial cells, showing that the effector EspFu is associated with increased bacterial attachment and enhanced epithelial colonization compared to the Tir-Nck pathway. Moreover, we also showed that actin pedestal formation can counterbalance the anti-inflammatory activity induced by EPEC, especially when driven by EspFu. Collectively, our findings provide new insights into virulence mechanisms employed by EPEC to colonize epithelial cells, as well as the host response to this enteric pathogen.
format	article
author	Fernando H. Martins Ashwani Kumar Cecilia M. Abe Eneas Carvalho Milton Nishiyama-Jr Chao Xing Vanessa Sperandio Waldir P. Elias
author_facet	Fernando H. Martins Ashwani Kumar Cecilia M. Abe Eneas Carvalho Milton Nishiyama-Jr Chao Xing Vanessa Sperandio Waldir P. Elias
author_sort	Fernando H. Martins
title	EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways
title_short	EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways
title_full	EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways
title_fullStr	EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways
title_full_unstemmed	EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways
title_sort	espfu-mediated actin assembly enhances enteropathogenic <italic toggle="yes">escherichia coli</italic> adherence and activates host cell inflammatory signaling pathways
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/12aa13d049e145149b9e0a0bf7ce0d36
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EspFu-Mediated Actin Assembly Enhances Enteropathogenic <italic toggle="yes">Escherichia coli</italic> Adherence and Activates Host Cell Inflammatory Signaling Pathways

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