Enigmatic roles of Vibrio cholerae hemolysin/cytolysin in the bacterial pathogenesis and host-pathogen interactions

Vibrio cholerae cytolysin (VCC; also known as V. cholerae hemolysin) is a β-barrel pore-forming toxin (β-PFT) secreted by the cholera pathogen V. cholerae. VCC acts to disrupt the selective permeability barrier function of the target cell membranes. Monomeric VCC molecules bind to and form heptameric transmembrane water-filled pores or channels in the lipid bilayer of the membranes, thus resulting in colloid-osmotic lysis of the target cells. Apart from its pore-forming function, VCC can activate an array of signaling cascades leading to the diverse responses that include programmed cell death, autophagy, inflammation, etc. VCC has been studied extensively focusing on the biochemical, biophysical, and structural aspects of the pore-formation mechanism. In contrast, the mechanistic basis of the VCC-mediated programmed cellular responses and their implications for bacterial pathogenesis and host-pathogen interaction processes have received less attention in the past. However, more recent studies have highlighted the crucial importance of the pore-formation-independent cellular responses for the V. cholerae pathogenesis process. Nevertheless, several questions regarding the pathophysiological contributions of VCC remain unanswered. In this minireview, we provide a brief account of the historical perspective of VCC in the context of V. cholerae pandemics, its pore-formation mechanism, and distinct cellular responses that could be evoked by this exotoxin in its target host cells. We also highlight some of the unanswered questions regarding its pathophysiological attributes and their potential contributions during the bacterial infection.