Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA

CagA, encoded by cytotoxin-associated gene A ( cagA ), is a major virulence factor of Helicobacter pylori , a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA -positive H. pylori may also be associated with diseases outside the stomach, although th...

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Published inScientific reports Vol. 6; no. 1; p. 18346
Main Authors Shimoda, Asako, Ueda, Koji, Nishiumi, Shin, Murata-Kamiya, Naoko, Mukai, Sada-atsu, Sawada, Shin-ichi, Azuma, Takeshi, Hatakeyama, Masanori, Akiyoshi, Kazunari
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 07.01.2016
Nature Publishing Group
Subjects
101/58
14
14/19
14/28
14/34
49/75
631/1647
631/326
64/60
Antigens, Bacterial - genetics
Antigens, Bacterial - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological Transport
Biomarkers
Cell Line
Cell size
Chromatography, Liquid
Epithelial cells
Exosomes
Exosomes - metabolism
Gastrointestinal diseases
Helicobacter Infections - complications
Helicobacter Infections - microbiology
Helicobacter pylori
Helicobacter pylori - physiology
Humanities and Social Sciences
Humans
Infections
multidisciplinary
Pathogens
Protein Transport
Science
Stomach
Stomach Neoplasms - etiology
Tandem Mass Spectrometry
Virulence Factors
Online AccessGet full text
ISSN2045-2322
2045-2322
DOI10.1038/srep18346

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Abstract CagA, encoded by cytotoxin-associated gene A ( cagA ), is a major virulence factor of Helicobacter pylori , a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA -positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patients infected with cagA -positive H. pylori (n = 4). We also found that gastric epithelial cells inducibly expressing CagA secrete exosomes containing CagA. Addition of purified CagA-containing exosomes to gastric epithelial cells induced an elongated cell shape, indicating that the exosomes deliver functional CagA into cells. These findings indicated that exosomes secreted from CagA-expressing gastric epithelial cells may enter into circulation, delivering CagA to distant organs and tissues. Thus, CagA-containing exosomes may be involved in the development of extragastric disorders associated with cagA -positive H. pylori infection.
AbstractList CagA, encoded by cytotoxin-associated gene A (cagA), is a major virulence factor of Helicobacter pylori, a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA-positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patients infected with cagA-positive H. pylori (n = 4). We also found that gastric epithelial cells inducibly expressing CagA secrete exosomes containing CagA. Addition of purified CagA-containing exosomes to gastric epithelial cells induced an elongated cell shape, indicating that the exosomes deliver functional CagA into cells. These findings indicated that exosomes secreted from CagA-expressing gastric epithelial cells may enter into circulation, delivering CagA to distant organs and tissues. Thus, CagA-containing exosomes may be involved in the development of extragastric disorders associated with cagA-positive H. pylori infection.
CagA, encoded by cytotoxin-associated gene A ( cagA ), is a major virulence factor of Helicobacter pylori , a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA -positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patients infected with cagA -positive H. pylori (n = 4). We also found that gastric epithelial cells inducibly expressing CagA secrete exosomes containing CagA. Addition of purified CagA-containing exosomes to gastric epithelial cells induced an elongated cell shape, indicating that the exosomes deliver functional CagA into cells. These findings indicated that exosomes secreted from CagA-expressing gastric epithelial cells may enter into circulation, delivering CagA to distant organs and tissues. Thus, CagA-containing exosomes may be involved in the development of extragastric disorders associated with cagA -positive H. pylori infection.
ArticleNumber 18346
Author Shimoda, Asako
Mukai, Sada-atsu
Murata-Kamiya, Naoko
Ueda, Koji
Sawada, Shin-ichi
Akiyoshi, Kazunari
Azuma, Takeshi
Nishiumi, Shin
Hatakeyama, Masanori
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  givenname: Asako
  surname: Shimoda
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  organization: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int’tech Center, Katsura
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  surname: Ueda
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  organization: Division of Biosciences, Functional Proteomics Center, Graduate School of Frontier Sciences, the University of Tokyo, CREST hall 1F, Institute of Medical Science, 4-6-1 Shirokanedai
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  organization: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku
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  surname: Murata-Kamiya
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  organization: Department of Microbiology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo
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  surname: Mukai
  fullname: Mukai, Sada-atsu
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  givenname: Shin-ichi
  surname: Sawada
  fullname: Sawada, Shin-ichi
  organization: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int’tech Center, Katsura
– sequence: 7
  givenname: Takeshi
  surname: Azuma
  fullname: Azuma, Takeshi
  organization: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku
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  givenname: Masanori
  surname: Hatakeyama
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  surname: Akiyoshi
  fullname: Akiyoshi, Kazunari
  organization: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int’tech Center, Katsura
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crossref_primary_10_1038_srep18346
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PublicationDate 2016-01-07
PublicationDateYYYYMMDD 2016-01-07
PublicationDate_xml – month: 01
  year: 2016
  text: 2016-01-07
  day: 07
PublicationDecade 2010
PublicationPlace London
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PublicationTitle Scientific reports
PublicationTitleAbbrev Sci Rep
PublicationTitleAlternate Sci Rep
PublicationYear 2016
Publisher Nature Publishing Group UK
Nature Publishing Group
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
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Snippet CagA, encoded by cytotoxin-associated gene A ( cagA ), is a major virulence factor of Helicobacter pylori , a gastric pathogen involved in the development of...
CagA, encoded by cytotoxin-associated gene A (cagA), is a major virulence factor of Helicobacter pylori, a gastric pathogen involved in the development of...
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StartPage 18346
SubjectTerms 101/58
14
14/19
14/28
14/34
49/75
631/1647
631/326
64/60
Antigens, Bacterial - genetics
Antigens, Bacterial - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological Transport
Biomarkers
Cell Line
Cell size
Chromatography, Liquid
Epithelial cells
Exosomes
Exosomes - metabolism
Gastrointestinal diseases
Helicobacter Infections - complications
Helicobacter Infections - microbiology
Helicobacter pylori
Helicobacter pylori - physiology
Humanities and Social Sciences
Humans
Infections
multidisciplinary
Pathogens
Protein Transport
Science
Stomach
Stomach Neoplasms - etiology
Tandem Mass Spectrometry
Virulence Factors
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Title Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA
URI https://link.springer.com/article/10.1038/srep18346
https://www.ncbi.nlm.nih.gov/pubmed/26739388
https://www.proquest.com/docview/1899038674
https://www.proquest.com/docview/1760892724
https://pubmed.ncbi.nlm.nih.gov/PMC4703974
Volume 6
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