Abstract
Pore-forming toxins (PFTs) are a distinct class of membrane-damaging cytolytic proteins that contribute significantly towards the virulence processes employed by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC) is a prominent member of the beta-barrel PFT (beta-PFT) family. It is secreted by most of the pathogenic strains of the intestinal pathogen V. cholerae. Owing to its potent membrane-damaging cell-killing activity, VCC is believed to play critical roles in V. cholerae pathogenesis, particularly in those strains that lack the cholera toxin. Large numbers of studies have explored the mechanistic basis of the cell-killing activity of VCC. Consistent with the beta-PFT mode of action, VCC has been shown to act on the target cells by forming transmembrane oligomeric beta-barrel pores, thereby leading to permeabilization of the target cell membranes. Apart from the pore-formation-induced direct cell-killing action, VCC exhibits the potential to initiate a plethora of signal transduction pathways that may lead to apoptosis, or may act to enhance the cell survival/activation responses, depending on the type of target cells. In this review, we will present a concise view of our current understanding regarding the multiple aspects of these cellular responses, and their underlying signaling mechanisms, evoked by VCC.
Highlights
Cholera is a deadly diarrhoeal disease caused by the gram negative bacterium Vibrio cholerae.The major virulence factor responsible for the induction of the pathophysiological responses duringV. cholerae infection is cholera toxin that is encoded by the CTX bacteriophage (CTXФ) [1].infections with V. cholerae strains lacking the cholera toxin has been found to cause cholera-like symptoms suggesting the implications of the additional virulence factors for the disease development [2,3].Many pathogenic strains of V. cholerae secrete a cytolysin/cytotoxin known as Vibrio cholerae cytolysin (VCC) [2,4,5]
Membrane pores formed by these toxins aid in the virulence processes, either by allowing bacterial components to enter into the target cells through the membrane pores, or by inducing colloid-osmotic lysis of the cells
TLR2 present on the cell surface that further instigates signaling cascades, activating the cells to respond to the toxin-induced assault
Summary
Cholera is a deadly diarrhoeal disease caused by the gram negative bacterium Vibrio cholerae. Bacterial β-PFTs are, in general, secreted as soluble monomeric proteins, and in contact with the target cell membrane they form transmembrane oligomeric pores [19]. Studies done with a wide array of cell types have shown that VCC causes cell death by forming transmembrane oligomeric β-barrel pores [22,23]. Sub-lytic concentrations of VCC, on the other hand, have been shown to modulate the cellular machinery in such a way that the target cells are activated to trigger pathways for promoting cell survival [25,26,27] Such diversity of responses induced by VCC suggests a significant yet unidentified role of this atypical β-PFT in the virulence mechanism of V. cholerae.
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