The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity.
The Helicobacter pylori toxin VacA causes vacuolar degeneration in mammalian cell lines in vitro and plays a key role in peptic ulcer disease. Two alleles, m1 and m2, of the mid-region of the vacA gene have been described, and the m2 cytotoxin always has been described as inactive in the in vitro HeLa cell assay. However, the m2 allele is associated with peptic ulcer and is prevalent in populations in which peptic ulcer and gastric cancer have high incidence. In this paper, we show that, despite the absence of toxicity on HeLa cells, the m2 cytotoxin is able to induce vacuolization in primary gastric cells and in other cell lines such as RK-13. The absence of Hela cell activity is due to an inability to interact with the cell surface, suggesting a receptor-mediated interaction. This result is consistent with the observation that the m2 allele is found in a population that has a high prevalence of peptic ulcer disease and gastric cancer. VacA is the first bacterial toxin described for which the same active subunit can be delivered by different receptor binding domains.
IRIS, Chiron S.p.A., via Fiorentina 1, 53100 Siena, Italy.
C
C
Pagliaccia
M
M
de Bernard
P
P
Lupetti
X
X
Ji
D
D
Burroni
T L
TL
Cover
E
E
Papini
R
R
Rappuoli
J L
JL
Telford
J M
JM
Reyrat
D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity*; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D001483:Base Sequence; D003603:Cytotoxins / Q000235:genetics / Q000502:physiology / Q000633:toxicity*; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D010437:Peptic Ulcer / Q000209:etiology / Q000382:microbiology; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology / Q000382:microbiology; D014162:Transfection; D014617:Vacuoles / Q000187:drug effects; D014774:Virulence
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D017931:DNA Primers; D004269:DNA, Bacterial; C074689:VacA protein, Helicobacter pylori