Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells.
Helicobacter pullorum, a bacterium initially isolated from poultry, has been associated with human digestive disorders. However, the factor responsible for its cytopathogenic effects on epithelial cells has not been formally identified. The cytopathogenic alterations induced by several human and avian H. pullorum strains were investigated on human intestinal epithelial cell lines. Moreover, the effects of the cytolethal distending toxin (CDT) were evaluated first by using a wild-type strain and its corresponding cdtB isogenic mutant and second by delivering the active CdtB subunit of the CDT directly into the cells. All of the H. pullorum strains induced cellular distending phenotype, actin cytoskeleton remodeling, and G2/M cell cycle arrest. These effects were dependent on the CDT, as they were (1) not observed in response to a cdtB isogenic mutant strain and (2) present in cells expressing CdtB. CdtB also induced an atypical delocalization of vinculin from focal adhesions to the perinuclear region, formation of cortical actin-rich large lamellipodia with an upregulation of cortactin, and decreased cellular adherence. In conclusion, the CDT of H. pullorum is responsible for major cytopathogenic effects in vitro, confirming its role as a main virulence factor of this emerging human pathogen.
Université de Bordeaux, Laboratoire de bactériologie, Centre National de Référence des Campylobacters et Hélicobacters.
Christine
C
Varon
Iulia
I
Mocan
Belgacem
B
Mihi
Christelle
C
Péré-Védrenne
Anriette
A
Aboubacar
Christine
C
Moraté
Mónica
M
Oleastro
François
F
Doignon
David
D
Laharie
Francis
F
Mégraud
Armelle
A
Ménard
D008841:Actin Cytoskeleton / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D049109:Cell Proliferation; D048430:Cell Shape; D018920:Coculture Techniques; D051356:Cortactin / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D019073:HT29 Cells; D016998:Helicobacter / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology*; D016086:Lentivirus / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011554:Pseudopodia / Q000378:metabolism / Q000382:microbiology*; D014162:Transfection; D016596:Vinculin / Q000378:metabolism*
D001427:Bacterial Toxins; C495868:CTTN protein, human; D051356:Cortactin; C067044:cytolethal distending toxin; D016596:Vinculin; D049452:Green Fluorescent Proteins
Helicobacter pullorum; actin; adherence; cortactin; cytolethal distending toxin; epithelial cells; isogenic mutant; lamellipodia; lentivirus; vinculin