The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface

ABSTRACT Many strains of Escherichia coli carry a 29,250-bp ETT2 pathogenicity island (PAI), which includes genes predicted to encode type III secretion system (T3SS) components. Because it is similar to the Salmonella pathogenicity island 1 (SPI-1) system, encoding a T3SS in Salmonella enterica, it...

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Autores principales:	Alexander Shulman, Yael Yair, Dvora Biran, Thomas Sura, Andreas Otto, Uri Gophna, Dörte Becher, Michael Hecker, Eliora Z. Ron
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	ETT2 Escherichia coli ExPEC secretion T3SS Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bc8d32c67f904760a8d5eebb8022b167
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spelling	oai:doaj.org-article:bc8d32c67f904760a8d5eebb8022b1672021-11-15T16:00:14ZThe <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface10.1128/mBio.01070-182150-7511https://doaj.org/article/bc8d32c67f904760a8d5eebb8022b1672018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01070-18https://doaj.org/toc/2150-7511ABSTRACT Many strains of Escherichia coli carry a 29,250-bp ETT2 pathogenicity island (PAI), which includes genes predicted to encode type III secretion system (T3SS) components. Because it is similar to the Salmonella pathogenicity island 1 (SPI-1) system, encoding a T3SS in Salmonella enterica, it was assumed that ETT2 also encodes a secretion system injecting effectors into host cells. This assumption was checked in E. coli serotype O2—associated with urinary tract infections and septicemia—which has an intact ETT2 gene cluster, in contrast to most strains in which this cluster carries deletions and mutations. A proteomic search did not reveal any putative secreted effector. Instead, the majority of the secreted proteins were identified as flagellar proteins. A deletion of the ETT2 gene cluster significantly reduced the secretion of flagellar proteins, resulting in reduced motility. There was also a significant reduction in the transcriptional level of flagellar genes, indicating that ETT2 affects the synthesis, rather than secretion, of flagellar proteins. The ETT2 deletion also resulted in additional major changes in secretion of fimbrial proteins and cell surface proteins, resulting in relative resistance to detergents and hydrophobic antibiotics (novobiocin), secretion of large amounts of outer membrane vesicles (OMVs), and altered multicellular behavior. Most important, the ETT2 deletion mutants were sensitive to serum. These major changes indicate that the ETT2 gene cluster has a global effect on cell surface and physiology, which is especially important for pathogenicity, as it contributes to the ability of the bacteria to survive serum and cause sepsis. IMPORTANCE Drug-resistant extraintestinal pathogenic E. coli (ExPEC) strains are major pathogens, especially in hospital- and community-acquired infections. They are the major cause of urinary tract infections and are often involved in septicemia with high mortality. ExPEC strains are characterized by broad-spectrum antibiotic resistance, and development of a vaccine is not trivial because the ExPEC strains include a large number of serotypes. It is therefore important to understand the virulence factors that are involved in pathogenicity of ExPEC and identify new targets for development of antibacterial drugs or vaccines. Such a target could be ETT2, a unique type III secretion system present (complete or in parts) in many ExPEC strains. Here, we show that this system has a major effect on the bacterial surface—it affects sensitivity to drugs, motility, and secretion of extracellular proteins and outer membrane vesicles. Most importantly, this system is important for serum resistance, a prerequisite for septicemia.Alexander ShulmanYael YairDvora BiranThomas SuraAndreas OttoUri GophnaDörte BecherMichael HeckerEliora Z. RonAmerican Society for MicrobiologyarticleETT2Escherichia coliExPECsecretionT3SSMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	ETT2 Escherichia coli ExPEC secretion T3SS Microbiology QR1-502
spellingShingle	ETT2 Escherichia coli ExPEC secretion T3SS Microbiology QR1-502 Alexander Shulman Yael Yair Dvora Biran Thomas Sura Andreas Otto Uri Gophna Dörte Becher Michael Hecker Eliora Z. Ron The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface
description	ABSTRACT Many strains of Escherichia coli carry a 29,250-bp ETT2 pathogenicity island (PAI), which includes genes predicted to encode type III secretion system (T3SS) components. Because it is similar to the Salmonella pathogenicity island 1 (SPI-1) system, encoding a T3SS in Salmonella enterica, it was assumed that ETT2 also encodes a secretion system injecting effectors into host cells. This assumption was checked in E. coli serotype O2—associated with urinary tract infections and septicemia—which has an intact ETT2 gene cluster, in contrast to most strains in which this cluster carries deletions and mutations. A proteomic search did not reveal any putative secreted effector. Instead, the majority of the secreted proteins were identified as flagellar proteins. A deletion of the ETT2 gene cluster significantly reduced the secretion of flagellar proteins, resulting in reduced motility. There was also a significant reduction in the transcriptional level of flagellar genes, indicating that ETT2 affects the synthesis, rather than secretion, of flagellar proteins. The ETT2 deletion also resulted in additional major changes in secretion of fimbrial proteins and cell surface proteins, resulting in relative resistance to detergents and hydrophobic antibiotics (novobiocin), secretion of large amounts of outer membrane vesicles (OMVs), and altered multicellular behavior. Most important, the ETT2 deletion mutants were sensitive to serum. These major changes indicate that the ETT2 gene cluster has a global effect on cell surface and physiology, which is especially important for pathogenicity, as it contributes to the ability of the bacteria to survive serum and cause sepsis. IMPORTANCE Drug-resistant extraintestinal pathogenic E. coli (ExPEC) strains are major pathogens, especially in hospital- and community-acquired infections. They are the major cause of urinary tract infections and are often involved in septicemia with high mortality. ExPEC strains are characterized by broad-spectrum antibiotic resistance, and development of a vaccine is not trivial because the ExPEC strains include a large number of serotypes. It is therefore important to understand the virulence factors that are involved in pathogenicity of ExPEC and identify new targets for development of antibacterial drugs or vaccines. Such a target could be ETT2, a unique type III secretion system present (complete or in parts) in many ExPEC strains. Here, we show that this system has a major effect on the bacterial surface—it affects sensitivity to drugs, motility, and secretion of extracellular proteins and outer membrane vesicles. Most importantly, this system is important for serum resistance, a prerequisite for septicemia.
format	article
author	Alexander Shulman Yael Yair Dvora Biran Thomas Sura Andreas Otto Uri Gophna Dörte Becher Michael Hecker Eliora Z. Ron
author_facet	Alexander Shulman Yael Yair Dvora Biran Thomas Sura Andreas Otto Uri Gophna Dörte Becher Michael Hecker Eliora Z. Ron
author_sort	Alexander Shulman
title	The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface
title_short	The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface
title_full	The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface
title_fullStr	The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface
title_full_unstemmed	The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface
title_sort	<named-content content-type="genus-species">escherichia coli</named-content> type iii secretion system 2 has a global effect on cell surface
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/bc8d32c67f904760a8d5eebb8022b167
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The <named-content content-type="genus-species">Escherichia coli</named-content> Type III Secretion System 2 Has a Global Effect on Cell Surface

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