Perfringolysin O and related cholesterol-dependent cytolysins: mechanism of pore formation

Many Gram-positive and a few Gram-negative bacteria express a cholesterol-dependent cytolysin (CDC). CDCs comprise a large family of structurally and mechanistically related toxins defined by their ability to form large oligomeric pore structures on membranes and dependence on host membrane cholesterol for their pore-forming activity. Following secretion as soluble monomers, CDCs bind membranes via a host cell receptor and are converted to a membrane-bound complex comprised of multiple monomers. This process has been the subject of extensive research. This chapter focuses primarily on studies of the past decade that have revealed insights into the molecular aspects of the CDC pore-forming mechanism.