Cholesterol-Dependent Cytolysins and Perforin: Similar Pore-Forming Mechanisms in Pathogenic Attack and Human Immune Defense

MACPF/CDCs proteins are a huge family of pore-forming proteins present from the bacteria to the human genera. Cholesterol-dependent cytolysins (CDCs) are a family of toxins that participate in bacterial infection pathway at the membrane level. Great interest in this family is due to their similarity, in structure and in pore-forming mechanism, with some human immune system proteins (MACPF). We focused our attention particularly on two bacterial CDCs, Perfringolysin O and Listeriolysin O, and on the human protein Perforin, which is involved in the apoptotic pathway facilitating Granzyme release. In the literature, two possible configurations of CDCs and Perforin pores are proposed: ring and arc structures that could have different implications on the biological mechanism of action of these pore-forming proteins. By electrophysiological measurements and atomic force microscopy technique on different artificial membrane, we are able to enrich the ring and the arc fraction and demonstrate that both kinds of pore are active, i.e. conduct ions. Thus, my PhD work underlines two physiological structures which are involved in several ways, more than merely by disrupting membrane integrity, in pathogenic attack (bacterial CDCs proteins) as well as in immune response (human Perforin proteins).