Vibrio cholerae cytolysin: Multiple facets of the membrane interaction mechanism of a β‐barrel pore‐forming toxin

Abstract

Vibrio cholerae cytolysin (VCC) is a membrane-damaging protein toxin with potent cytolytic/cytotoxic activity against wide range of eukaryotic cells. VCC is a β-barrel pore-forming toxin (β-PFT), and it inflicts damage to the target cell membranes by forming transmembrane heptameric β-barrel pores. To exert pore-forming activity, VCC must bind to the cell membranes in an efficient manner. Efficient interaction with the cell membranes is an essential pre-requisite to trigger subsequent structural/conformational and organizational changes in the toxin molecules leading toward formation of the transmembrane oligomeric β-barrel pores. Based on the large numbers of studies investigating the mode of action of VCC, it is now evident that VCC is capable of using multiple distinct mechanisms to recognize and bind to the membrane components and cell surface molecules. In this review article, we present an overview of our current understanding regarding the membrane interaction mechanisms of VCC, and their functional implications for the pore-forming activity of the toxin. © 2018 IUBMB Life, 70(4):260-266, 2018.

At the Gate of Mutualism: Identification of Genomic Traits Predisposing to Insect-Bacterial Symbiosis in Pathogenic Strains of the Aphid Symbiont Serratia symbiotica

“…The genes bsaQ and bsaX , also found in all three genomes, code for T3SS effector proteins that have been found essential for intracellular survival of Burkholderia pseudomallei in host cells ( Muangsombut et al., 2008 ). Few toxin production-related genes were detected, with the exception of genes encoding the hemolytic protein hemolysin III and the pore-forming toxin Vibrio cholerae cytolysin (VCC) encoded by hlyA , both associated with a cytolytic/cytotoxic activity against wide range of eukaryotic cells ( Baida and Kuzmin, 1996 ; Kathuria and Chattopadhyay, 2018 ). Intriguingly, all strains seem to have retained some ability to synthesize T4SS effectors while, with the exception of SsApa8A1, they did not retain any complete T4SS.…”

The <em>Vibrio cholerae </em>Cytotoxin (VCC) Simultaneously Activates Responses of Death, Inflammation (NF-&kappa;B) and Survival (AP-1) through the MAPK Signaling in Human Macrophages THP-1

“…A 96-well plate with 1x10 6 Vero cells was seeded with supplemented DMEM and incubated at 37°C in humidified atmosphere with 5% overnight CO 2 , then fresh medium was added to the cells without FBS. One volume of the concentrated toxin was added to the first well of the plate, then 1:2 serial dilutions were made in the following wells.…”

“…Once released to the bacterial surroundings, due to its transmembrane domain the monomeric form of VCC commonly gets its way to insert itself on the cytoplasmic membrane of the target cell. In the cytoplasmic membrane, monomers follow one to another, until forming a molecular pore of approximately 1-2 nm in diameter [5][6][7], a self-assembled heptameric holotoxin, in the shape of a β-barrel structure. Numerous heptameric pores, get to disrupt the membrane permeability [8,9].…”

Vibrio vulnificus Hemolysin: Biological Activity, Regulation of vvhA Expression, and Role in Pathogenesis

“…More researchers contend that infections may be driven more by factors associated with host susceptibility than the virulence of V. vulnificus (1,12). Besides V. vulnificus, the hemolysins produced by Vibrio cholerae and Gram-positive species such as Streptococcus pneumoniae, Streptococcus suis, Bacillus Cereus, have been extensively reviewed (21)(22)(23). Like most Gram-negative bacteria, the X-ray crystal structure of VVH remains unknown.…”