Vaginolysin Drives Epithelial Ultrastructural Responses to Gardnerella vaginalis
Tara M. Randis,Joanne Zaklama,Timothy J. LaRocca,Ferdinand C. O. Los,Emma L. Lewis,Purnahamsi Desai,Ryan Rampersaud,Fábio E. Amaral,Adam J. Ratner +8 more
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TLDR
Results indicate that the formation of functional pores drives the observed ultrastructural rearrangements in vaginal and cervical epithelial cells, and VLY-induced epithelial cell membrane blebbing in the vaginal mucosa may play a role in the pathogenesis of BV.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-β-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.read more
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Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis
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Interaction of Gardnerella vaginalis and Vaginolysin with the Apical versus Basolateral Face of a Three-Dimensional Model of Vaginal Epithelium.
TL;DR: Results from this study suggest that while G. vaginalis may grow on the apical face of the vaginal epithelium, its VLY toxin does not target these cells in this model and may suggest an explanation for the lack of an overt immune response to this organism.
References
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Caspase-1 Activation of Lipid Metabolic Pathways in Response to Bacterial Pore-Forming Toxins Promotes Cell Survival
Laure Gurcel,Laurence Abrami,Stephen E. Girardin,Jürg Tschopp,F. Gisou van der Goot,F. Gisou van der Goot +5 more
TL;DR: It is found that when rendered proteolytic in this context caspase-1 induces the activation of the central regulators of membrane biogenesis, the Sterol Regulatory Element Binding Proteins (SREBPs), which in turn promote cell survival upon toxin challenge possibly by facilitating membrane repair.
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Cholesterol-Dependent Cytolysins, a Family of Versatile Pore-Forming Toxins
TL;DR: The cholesterol-dependent cytolysins are a large family of pore-forming toxins that are produced by more than 20 species from the genera Clostridium, Streptococcus, Listeria, Bacillus, and Arcanobacterium.
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Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes.
TL;DR: It is strongly suggested that hemolysin is a major virulence factor implicated in the intracellular growth of L. monocytogenes, which is unable to grow in host tissues and were rapidly eliminated from the spleen and liver of infected mice.