Vaginolysin drives epithelial ultrastructural responses to Gardnerella vaginalis.
Infect Immun
; 81(12): 4544-50, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-24082080
ABSTRACT
Gardnerella vaginalis, the bacterial species most frequently isolated from women with bacterial vaginosis (BV), produces a cholesterol-dependent cytolysin (CDC), vaginolysin (VLY). At sublytic concentrations, CDCs may initiate complex signaling cascades crucial to target cell survival. Using live-cell imaging, we observed the rapid formation of large membrane blebs in human vaginal and cervical epithelial cells (VK2 and HeLa cells) exposed to recombinant VLY toxin and to cell-free supernatants from growing liquid cultures of G. vaginalis. Binding of VLY to its human-specific receptor (hCD59) is required for bleb formation, as antibody inhibition of either toxin or hCD59 abrogates this response, and transfection of nonhuman cells (CHO-K1) with hCD59 renders them susceptible to toxin-induced membrane blebbing. Disruption of the pore formation process (by exposure to pore-deficient toxoids or pretreatment of cells with methyl-ß-cyclodextrin) or osmotic protection of target cells inhibits VLY-induced membrane blebbing. These results indicate that the formation of functional pores drives the observed ultrastructural rearrangements. Rapid bleb formation may represent a conserved response of epithelial cells to sublytic quantities of pore-forming toxins, and VLY-induced epithelial cell membrane blebbing in the vaginal mucosa may play a role in the pathogenesis of BV.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Proteínas Bacterianas
/
Toxinas Bacterianas
/
Gardnerella vaginalis
/
Vaginosis Bacteriana
/
Extensiones de la Superficie Celular
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Infect Immun
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos