Chapter 36 - Repertoire and general features of the family of cholesterol-dependent cytolysins

Abstract

The cholesterol-dependent cytolysins (CDCs), also called cholesterol-binding cytolysins, constitute a group of 50- to 60-kDa single-chain, pore-forming bacterial protein toxins previously designated "sulfhydryl" (or "thiol-activated)" cytolysins. This group of structurally, antigenically, and functionally related cytolysins constitutes the largest family of bacterial protein toxins produced by Gram-positive bacteria. CDCs are lethal to animals and highly lytic towards eucaryotic cells, including erythrocytes. Their lytic and lethal properties are suppressed by sulfhydryl-group blocking agents and reversibly restored by thiols or other reducing agents. This chapter classifies and lists the general features of this family of cholesterol-dependant cytolysins. Important progress has been made in the past five years with regard to the mechanisms of toxin insertion and oligomerization in target cells in relation to membrane cholesterol and the genetics and structural characteristics of these toxins. However, the role of certain CDCs in disease, particularly in inflammatory processes and probably in sepsis, remains poorly understood. Moreover, the involvement of CDCs in host-signaling pathways still requires further investigation. Finally, the potential use of certain CDCs as potent permeabilization probes in cell biology or as vaccines or novel therapeutical agents remains an important and promising issue.