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Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells
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Orientador(es)
Resumo(s)
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.
Descrição
Palavras-chave
Helicobacter pullorum Actin Adherence Cortactin Cytolethal Distending Toxin Epithelial Cells Isogenic Mutant Lamellipodia Lentivirus Vinculin Infecções Gastrointestinais
Contexto Educativo
Citação
J Infect Dis. 2014 Feb 15;209(4):588-99. doi: 10.1093/infdis/jit539
Editora
Oxford University Press/Infectious Diseases Society of America