Towards deciphering the Helicobacter pylori cytotoxin.
VacA, the major exotoxin produced by Helicobacter pylori, is composed of identical 87 kDa monomers that assemble into flower-shaped oligomers. The monomers can be proteolytically cleaved into two moieties, one of 37 and the other of 58 kDa, named P37 and P58 respectively. The most studied property of VacA is the alteration of intracellular vesicular trafficking in eukaryotic cells leading to the formation of large vacuoles containing markers of late endosomes and lysosomes. However, VacA also causes a reduction in transepithelial electrical resistance in polarized monolayers and forms ion channels in lipid bilayers. The ability to induce vacuoles is localized mostly but not entirely in P37, whereas P58 is mostly involved in cell targeting. Until recently, H. pylori isolates were classified as tox+ or tox-, depending on whether they induced vacuoles in HeLa cells or not. Today, we know that almost all strains are cytotoxic. The major difference between tox+ and tox- resides in the cell binding domain, which exists in two allelic forms, only one of which is toxic for HeLa cells. The two forms, named m1 and m2, are found predominantly in Western and Chinese isolates respectively.
Reyrat
J M
JM
IRIS, Chiron S.p.A., via Fiorentina 1, 53100 Siena, Italy. jmreyrat@pasteur.fr
Pelicic
V
V
Papini
E
E
Montecucco
C
C
Rappuoli
R
R
Telford
J L
JL
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D003603:Cytotoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D005798:Genes, Bacterial; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori