Cells treated with the VacA toxin from Helicobacter pylori develop large membrane-bound vacuoles that originate from the late endocytotic pathway. Using different experimental approaches, we showed that VacA can induce vacuoles by acting within the cell cytosol. Moreover, separation of VacA-induced vacuoles at an early stage of formation, using a novel isopycnic density ultracentrifugation method, allowed us to show that they resemble a hybrid compartment, containing elements of both late endosomes and lysosomes. Functional defects of the endocytotic pathway were also studied before any macroscopic vacuolation is evident. VacA-intoxicated cells degrade extracellular ligands with reduced efficiency and, at the same time, they secrete acidic hydrolases into the extracellular medium, normally sorted to lysosomes. All these findings indicate that VacA translocates into the cell cytosol where it causes a lesion of the late endosomal/lysosomal compartments, such that protein trafficking across this crucial cross-point is altered with consequences that may be relevant to the pathogenesis of gastroduodenal ulcers.

Centro CNR Biomembrane Università di Padova Italy

See more in PubMed

Int Immunol. 1996 May;8(5):625-40 PubMed

J Med Microbiol. 1996 Aug;45(2):84-9 PubMed

Cell. 1988 Oct 21;55(2):309-20 PubMed

Mol Microbiol. 1994 Apr;12(2):307-19 PubMed

J Biol Chem. 1995 Oct 13;270(41):23937-40 PubMed

J Cell Sci. 1997 Sep;110 ( Pt 17):2027-40 PubMed

J Biol Chem. 1992 Aug 5;267(22):15665-72 PubMed

Med J Aust. 1985 Apr 15;142(8):436-9 PubMed

J Exp Med. 1994 May 1;179(5):1653-58 PubMed

Cell. 1994 Jan 28;76(2):287-99 PubMed

Trends Biotechnol. 1994 Oct;12(10):420-6 PubMed

Infect Immun. 1996 Oct;64(10):4197-203 PubMed

Trends Cell Biol. 1996 Sep;6(9):329-32 PubMed

Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 PubMed

Annu Rev Cell Biol. 1993;9:129-61 PubMed

Trends Microbiol. 1993 Oct;1(7):255-60 PubMed

Mol Microbiol. 1993 Jan;7(2):323-7 PubMed

EMBO J. 1997 Jan 2;16(1):15-24 PubMed

J Cell Biol. 1994 May;125(3):573-82 PubMed

J Cell Sci. 1996 Apr;109 ( Pt 4):749-62 PubMed

J Biol Chem. 1994 Apr 8;269(14):10566-73 PubMed

Annu Rev Cell Biol. 1989;5:483-525 PubMed

J Cell Biol. 1996 May;133(4):801-7 PubMed

Nature. 1995 Feb 23;373(6516):663-4 PubMed

Curr Biol. 1996 Feb 1;6(2):183-8 PubMed

Eur J Biochem. 1995 Dec 15;234(3):947-52 PubMed

Lancet. 1983 Jun 4;1(8336):1273-5 PubMed

J Biol Chem. 1997 Oct 3;272(40):25022-8 PubMed

J Med Microbiol. 1992 Dec;37(6):389-95 PubMed

Lancet. 1993 May 29;341(8857):1359-62 PubMed

Science. 1994 Feb 11;263(5148):802-5 PubMed

J Biol Chem. 1992 May 25;267(15):10570-5 PubMed

Infect Immun. 1995 Oct;63(10):4154-60 PubMed

Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14648-53 PubMed

Annu Rev Biochem. 1986;55:167-93 PubMed

J Cell Biol. 1997 Aug 25;138(4):759-69 PubMed

Infect Immun. 1995 Jan;63(1):94-8 PubMed

Infect Immun. 1994 May;62(5):1557-65 PubMed

J Cell Biol. 1983 Jul;97(1):1-5 PubMed

Curr Biol. 1995 Jun 1;5(6):635-42 PubMed

FEBS Lett. 1994 Jun 6;346(1):92-8 PubMed

J Med Microbiol. 1988 Jun;26(2):93-9 PubMed

Nature. 1997 Aug 21;388(6644):724-5 PubMed

J Biol Chem. 1997 Oct 3;272(40):25339-44 PubMed

Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9720-4 PubMed

Mol Microbiol. 1997 Nov;26(4):665-74 PubMed

Science. 1995 Mar 17;267(5204):1655-8 PubMed

Infect Immun. 1993 Apr;61(4):1427-31 PubMed

N Engl J Med. 1994 May 5;330(18):1267-71 PubMed

J Cell Sci. 1992 Jul;102 ( Pt 3):515-26 PubMed

A meeting of good friends: when the cell biology of prokaryotes and eukaryotes meet