Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin

ABSTRACT Remodeling of the host cytoskeleton is a common strategy employed by bacterial pathogens. Although there is vigorous investigation of the cell biology underlying these bacterially mediated cytoskeleton modifications, knowledge of the plasticity and dynamics of the bacterial signaling networ...

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Autores principales:	Charley C. Gruber, Vanessa Sperandio
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/13b0adbb06ed42cabff07264d0af14e3
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spelling	oai:doaj.org-article:13b0adbb06ed42cabff07264d0af14e32021-11-15T15:45:10ZPosttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin10.1128/mBio.01025-132150-7511https://doaj.org/article/13b0adbb06ed42cabff07264d0af14e32014-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01025-13https://doaj.org/toc/2150-7511ABSTRACT Remodeling of the host cytoskeleton is a common strategy employed by bacterial pathogens. Although there is vigorous investigation of the cell biology underlying these bacterially mediated cytoskeleton modifications, knowledge of the plasticity and dynamics of the bacterial signaling networks that regulate the expression of genes necessary for these phenotypes is lacking. Enterohemorrhagic Escherichia coli attaches to enterocytes, forming pedestal-like structures. Pedestal formation requires the expression of the locus-of-enterocyte-effacement (LEE) and espFu genes. The LEE encodes a molecular syringe, a type III secretion system (T3SS) used by pathogens to translocate effectors such as EspFu into the host cell. By using a combination of genetic, biochemical, and cell biology approaches, we show that pedestal formation relies on posttranscriptional regulation by two small RNAs (sRNAs), GlmY and GlmZ. The GlmY and GlmZ sRNAs are unique; they have extensive secondary structures and work in concert. Although these sRNAs may offer unique insights into RNA and posttranscriptional biology, thus far, only one target and one mechanism of action (exposure of the ribosome binding site from the glmS gene to promote its translation) has been described. Here we uncovered new targets and two different molecular mechanisms of action of these sRNAs. In the case of EspFu expression, they promote translation by cleavage of the transcript, while in regard to the LEE, they promote destabilization of the mRNA. Our findings reveal that two unique sRNAs act in concert through different molecular mechanisms to coordinate bacterial attachment to mammalian cells. IMPORTANCE Pathogens evolve by horizontal acquisition of pathogenicity islands. We describe here how two sRNAs, GlmY and GlmZ, involved in cellular metabolism and cellular architecture, through the posttranscriptional control of GlmS (the previously only known target of GlmY and GlmZ), which controls amino sugar synthesis, have been coopted to modulate the expression of virulence. These sRNAs quickly allow for plasticity in gene expression in order for enterohemorrhagic Escherichia coli to fine-tune the expression of its complex type III secretion machinery and its effectors to promote bacterial attachment and subsequent actin rearrangement on host cells. Pedestal formation is a very dynamic process. Many of the genes necessary for pedestal formation are located within the same operon to evolutionarily guarantee that they are inherited together. However, it is worth noting that within these operons, several genes need to yield more proteins than others and that these differences cannot be efficiently regulated at the transcriptional level.Charley C. GruberVanessa SperandioAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 1 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Charley C. Gruber Vanessa Sperandio Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin
description	ABSTRACT Remodeling of the host cytoskeleton is a common strategy employed by bacterial pathogens. Although there is vigorous investigation of the cell biology underlying these bacterially mediated cytoskeleton modifications, knowledge of the plasticity and dynamics of the bacterial signaling networks that regulate the expression of genes necessary for these phenotypes is lacking. Enterohemorrhagic Escherichia coli attaches to enterocytes, forming pedestal-like structures. Pedestal formation requires the expression of the locus-of-enterocyte-effacement (LEE) and espFu genes. The LEE encodes a molecular syringe, a type III secretion system (T3SS) used by pathogens to translocate effectors such as EspFu into the host cell. By using a combination of genetic, biochemical, and cell biology approaches, we show that pedestal formation relies on posttranscriptional regulation by two small RNAs (sRNAs), GlmY and GlmZ. The GlmY and GlmZ sRNAs are unique; they have extensive secondary structures and work in concert. Although these sRNAs may offer unique insights into RNA and posttranscriptional biology, thus far, only one target and one mechanism of action (exposure of the ribosome binding site from the glmS gene to promote its translation) has been described. Here we uncovered new targets and two different molecular mechanisms of action of these sRNAs. In the case of EspFu expression, they promote translation by cleavage of the transcript, while in regard to the LEE, they promote destabilization of the mRNA. Our findings reveal that two unique sRNAs act in concert through different molecular mechanisms to coordinate bacterial attachment to mammalian cells. IMPORTANCE Pathogens evolve by horizontal acquisition of pathogenicity islands. We describe here how two sRNAs, GlmY and GlmZ, involved in cellular metabolism and cellular architecture, through the posttranscriptional control of GlmS (the previously only known target of GlmY and GlmZ), which controls amino sugar synthesis, have been coopted to modulate the expression of virulence. These sRNAs quickly allow for plasticity in gene expression in order for enterohemorrhagic Escherichia coli to fine-tune the expression of its complex type III secretion machinery and its effectors to promote bacterial attachment and subsequent actin rearrangement on host cells. Pedestal formation is a very dynamic process. Many of the genes necessary for pedestal formation are located within the same operon to evolutionarily guarantee that they are inherited together. However, it is worth noting that within these operons, several genes need to yield more proteins than others and that these differences cannot be efficiently regulated at the transcriptional level.
format	article
author	Charley C. Gruber Vanessa Sperandio
author_facet	Charley C. Gruber Vanessa Sperandio
author_sort	Charley C. Gruber
title	Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin
title_short	Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin
title_full	Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin
title_fullStr	Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin
title_full_unstemmed	Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin
title_sort	posttranscriptional control of microbe-induced rearrangement of host cell actin
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/13b0adbb06ed42cabff07264d0af14e3
work_keys_str_mv	AT charleycgruber posttranscriptionalcontrolofmicrobeinducedrearrangementofhostcellactin AT vanessasperandio posttranscriptionalcontrolofmicrobeinducedrearrangementofhostcellactin
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Posttranscriptional Control of Microbe-Induced Rearrangement of Host Cell Actin

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