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

• Published in: Scientific 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
• Language: English
• 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18346

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.