title: Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA.
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.
authors.affiliation: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Shimoda
authors.affiliation: 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, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.affiliation: Department of Microbiology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Murata-Kamiya
authors.affiliation: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan.
authors.forename: Sada-Atsu
authors.initials: SA
authors.lastname: Mukai
authors.affiliation: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Sawada
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.affiliation: Department of Microbiology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatakeyama
authors.affiliation: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Bio-nanotransporter Project, Katsura Int'tech Center, Katsura, Nishikyo-ku, Kyoto 615-8530, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Akiyoshi
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D015415:Biomarkers; D002460:Cell Line; D002853:Chromatography, Liquid; D055354:Exosomes / Q000378:metabolism*; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D021381:Protein Transport; D013274:Stomach Neoplasms / Q000209:etiology; D053719:Tandem Mass Spectrometry; D037521:Virulence Factors
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori