Membrane-Damaging Toxins: Pore Formation

Abstract

The chapter discusses bona fide pore-forming toxins (PFTs) with the exception of RTX toxins. The role of PFTs in bacterial pathogenesis are discussed first; then their general mode of action are outlined, and the events that lead to pore formation are described at the structural level, using two examples, the PFTs from Staphylococcus aureus and the cholesterol-dependent toxins (CDTs). Finally, some of the consequences of pore formation are reviewed. Most PFTs are able to form pores in artificial membranes such as liposomes. This allowed researchers to study the mechanisms that lead to pore formation in great detail using in vitro approaches. Staphylococcus aureus secretes a variety of membrane-damaging toxins, including the α-hemolysin and the bicomponent leukotoxins, the active toxin of which comprises the combination of two similar subtype proteins. VacA was recently found to form small anion-selective, voltage-dependent channels in biological membranes at acidic pH. A variety of PFTs were also shown to trigger the release of calcium from intracellular stores (e.g., staphylococcal PFTs, aerolysin, and streptolysin O). By unknown mechanisms, these toxins lead to activation of G proteins, production of inositol(1,4,5)-triphosphate, and opening of calcium channels in the endoplasmic reticulum. Pore formation in the plasma membrane also allows entry of extracellular calcium.