Reduced intracellular survival of Helicobacter pylori vacA mutants in comparison with their wild-types indicates the role of VacA in pathogenesis

TY - JOUR

T1 - Reduced intracellular survival of Helicobacter pylori vacA mutants in comparison with their wild-types indicates the role of VacA in pathogenesis

AU - Petersen, Andreas Munk

AU - Sørensen, Kristine

AU - Blom, Jens

AU - Krogfelt, Karen Angeliki

PY - 2001/4/2

Y1 - 2001/4/2

N2 - The vacuolating cytotoxin VacA of Helicobacter pylori plays an important but yet unknown role in pathogenesis. We studied the impact of the vacuolating cytotoxin on H. pylori invasion of and survival within AGS cells (human gastric cell line derived from an antral adenocarcinoma). Isogenic vacA and cagA mutants were constructed in a wild-type clinical isolate H. pylori, AF4. An H. pylori VacA-deficient mutant, AF4(vacA::kan), was cultured in significantly lower numbers from AGS cells after 24 h incubation with gentamicin added to the culture medium than were the type I wild-type strain AF4 (P < 0.03) and an isogenic cagA mutant (P < 0.01). Complementation of the AF4 vacA mutant with broth culture supernatant from wild-type AF4 improved the intracellular survival of the vacA mutant. We conclude that H. pylori's vacuolating cytotoxin improves the intracellular survival of H. pylori within AGS cells, suggesting the role of the vacuolating cytotoxin in H. pylori pathogenesis.

AB - The vacuolating cytotoxin VacA of Helicobacter pylori plays an important but yet unknown role in pathogenesis. We studied the impact of the vacuolating cytotoxin on H. pylori invasion of and survival within AGS cells (human gastric cell line derived from an antral adenocarcinoma). Isogenic vacA and cagA mutants were constructed in a wild-type clinical isolate H. pylori, AF4. An H. pylori VacA-deficient mutant, AF4(vacA::kan), was cultured in significantly lower numbers from AGS cells after 24 h incubation with gentamicin added to the culture medium than were the type I wild-type strain AF4 (P < 0.03) and an isogenic cagA mutant (P < 0.01). Complementation of the AF4 vacA mutant with broth culture supernatant from wild-type AF4 improved the intracellular survival of the vacA mutant. We conclude that H. pylori's vacuolating cytotoxin improves the intracellular survival of H. pylori within AGS cells, suggesting the role of the vacuolating cytotoxin in H. pylori pathogenesis.

KW - Helicobacter pylori

KW - Intracellular

KW - VacA

UR - http://www.scopus.com/inward/record.url?scp=0035074519&partnerID=8YFLogxK

U2 - 10.1016/S0928-8244(00)00246-7

DO - 10.1016/S0928-8244(00)00246-7

M3 - Journal article

C2 - 11267841

AN - SCOPUS:0035074519

SN - 0928-8244

VL - 30

SP - 103

EP - 108

JO - FEMS Immunology and Medical Microbiology

JF - FEMS Immunology and Medical Microbiology

IS - 2

ER -