Low pH activates the vacuolating toxin of Helicobacter pylori, which becomes acid and pepsin resistant.
The protein toxin VacA, produced by cytotoxic strains of Helicobacter pylori, causes a vacuolar degeneration of cells, which eventually die. VacA is strongly activated by a short exposure to acidic solutions in the pH 1.5-5.5 range, followed by neutralization. Activated VacA has different CD and fluorescence spectra and a limited proteolysis fragmentation pattern from VacA kept at neutral pH. Moreover, activated VacA is resistant to pH 1.5 and to pepsin. The relevance of these findings to pathogenesis of H. pylori-induced gastrointestinal ulcers is discussed.
de Bernard
M
M
Centro Consiglio Nazionale delle Ricerche di Biomembrane, Università di Padova, Italy.
Papini
E
E
de Filippis
V
V
Gottardi
E
E
Telford
J
J
Manetti
R
R
Fontana
A
A
Rappuoli
R
R
Montecucco
C
C
D001426:Bacterial Proteins / Q000737:chemistry* / Q000633:toxicity; D002942:Circular Dichroism; D003603:Cytotoxins / Q000737:chemistry* / Q000633:toxicity; D006367:HeLa Cells; D016480:Helicobacter pylori; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010434:Pepsin A / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D011402:Pronase; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D001426:Bacterial Proteins; D003603:Cytotoxins; D010446:Peptide Fragments; C074689:VacA protein, Helicobacter pylori; D010434:Pepsin A; D011402:Pronase