Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells.
Helicobacter pylori, a common pathogen that causes chronic gastritis and cancer, has evolved to establish persistent infections in the human stomach. Epidemiological evidence suggests that H. pylori with both highly active vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), the major virulence factors, has an advantage in adapting to the host environment. However, the mechanistic relationship between VacA and CagA remains obscure. Here, we report that CagA interferes with eukaryotic endocytosis, as revealed by genome-wide screening in yeast. Moreover, CagA suppresses pinocytic endocytosis and the cytotoxicity of VacA in gastric epithelial cells without affecting clathrin-dependent endocytosis. Our data suggest that H. pylori secretes VacA to attack distant host cells while injecting CagA into the gastric epithelial cells to which the bacteria are directly attached, thereby protecting these attached host cells from the cytotoxicity of VacA and creating a local ecological niche. This mechanism might allow H. pylori to balance damage to one population of host cells with the preservation of another, allowing for persistent infection.
Akada
Junko K
JK
Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Aoki
Hiroki
H
Torigoe
Yuji
Y
Kitagawa
Takao
T
Kurazono
Hisao
H
Hoshida
Hisashi
H
Nishikawa
Jun
J
Terai
Shuji
S
Matsuzaki
Masunori
M
Hirayama
Toshiya
T
Nakazawa
Teruko
T
Akada
Rinji
R
Nakamura
Kazuyuki
K
D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D003911:Dextrans / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D005800:Genes, Fungal / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D010873:Pinocytosis; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003911:Dextrans; D014168:Transferrin; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori