Helicobacter pylori VacA cytotoxin associated with the bacteria increases epithelial permeability independently of its vacuolating activity.
Polarized epithelial monolayers of Madin-Darby canine kidney (MDCK) cells were used to study the pathogenicity of Helicobater pylori, with an emphasis on the effect of VacA. The adherence of H. pylori to MDCK monolayers resulted in a decrease in trans-epithelial resistance (TER) across the cell monolayer. Isogenic vacA mutants did not lower the TER, demonstrating that the effect is strictly linked to the action of the toxin. A similar effect was observed with all VacA-producing strains, including those producing m2 toxins that are inactive in the vacuolating assay. In contrast to that seen with purified toxin, TER decrease was not enhanced by acid pH, which may indicate that the toxin associated to the bacterial surface is possibly in a monomeric state and therefore does not require a pH-induced conformation to be active. These data raise the possibility that one role of VacA in ulcerogenesis may consist of increasing the paracellular permeability of the gastric epithelium.
Pelicic
Vladimir
V
Dipartimento di Scienze Biomediche, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Reyrat
Jean-Marc
JM
IRIS, Chiron-SpA, Via Fiorentina 1, 53100 Siena, Italy.
Sartori
Lucia
L
Dipartimento di Scienze Biomediche, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Pagliaccia
Cristina
C
IRIS, Chiron-SpA, Via Fiorentina 1, 53100 Siena, Italy.
Rappuoli
Rino
R
IRIS, Chiron-SpA, Via Fiorentina 1, 53100 Siena, Italy.
Telford
John L
JL
IRIS, Chiron-SpA, Via Fiorentina 1, 53100 Siena, Italy.
Montecucco
Cesare
C
Dipartimento di Scienze Biomediche, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Papini
Emanuele
E
D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability; D016764:Cell Polarity; D003603:Cytotoxins / Q000502:physiology*; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000382:microbiology*; D005753:Gastric Mucosa / Q000382:microbiology / Q000503:physiopathology; D005756:Gastritis / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000378:metabolism / Q000472:pathogenicity*; D007668:Kidney; D013276:Stomach Ulcer / Q000382:microbiology / Q000503:physiopathology; D014617:Vacuoles / Q000502:physiology
D001426:Bacterial Proteins; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori