Brefeldin A enhances Helicobacter pylori vacuolating cytotoxin-induced vacuolation of epithelial cells.
Intracellular VacA localises to the vacuolar (late endosome/lysosome) membrane, but little is known about the trafficking of the toxin beyond this region. We show that the Golgi-disturbing agent brefeldin A (BFA) enhances VacA-induced vacuolation of epithelial cells by Helicobacter pylori co-culture and, importantly, BFA treatment induces vacuolation by less toxic forms of VacA. The effect is BFA dose-dependent and occurs within 2.5 h. These data suggest that VacA may be routed deeper within the cell than the vacuole, and that vacuolation is minimised when this occurs efficiently. This may explain why some forms of VacA do not cause vacuolation and why vacuolation is minimal at the low bacteria:cell ratios observed in vivo.
Argent
Richard H
RH
Institute of Infection, Immunity and Inflammation, and the Wolfson Digestive Diseases Centre, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK. richard.argent@nottingham.ac.uk
McGarr
Christine
C
Atherton
John C
JC
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity; D020126:Brefeldin A / Q000494:pharmacology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology* / Q000473:pathology*; D006056:Golgi Apparatus / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D008853:Microscopy; D009499:Neutral Red / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D014617:Vacuoles / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C074689:VacA protein, Helicobacter pylori; D020126:Brefeldin A; D009499:Neutral Red