Defense and death responses to pore forming toxins

Abstract

Pore forming toxins (PFT) are important virulence factors produced by bacteria to kill eukaryotic cells by forming holes in the cellular membrane. They represent a diverse group of proteins with a wide range of target cells. Although the amino acid sequence is not conserved among the different PFT, many of them share some aspects of their mechanism of action. In general, the mode of action of PFT involves receptor recognition, activation by proteases, and aggregation into oligomeric-structures that insert into the membrane to form ionic pores. Beside the pore formation activity, PFT may have other effects during its interaction with their target cells such as intra-cellular signaling or transport of other enzymatic components, as in the case of anthrax or diphtheria toxins produced by Bacillus anthracis and Corynebacterium diphtheria, respectively (Parker and Feil, 2005). Although PFT have evolved as a pathogenic mechanism, some of them have great impact in society since they have different applications in biotechnology or are used as therapeutic agents, or as tools in the study of cell biology (Schiavo and van der Goot, 2001). On the other side, their target organisms have evolved different mechanisms to counter toxin action. Understanding the mechanism of action of PFT as well as the host responses to toxin action would provide ways to deal with these pathogens or with emerging pathogens and more importantly to improve the action of toxins that have biotechnological applications. In this review we will describe the intracellular effects induced by some PFT and the cellular responses evolved by eukaryotic cell to overcome PFT action.