Surface properties of bacterial sulfhydryl-activated cytolytic toxins. Interaction with monomolecular films of phosphatidylcholine and various sterols.

Sulfhydryl-activated cytolysins are a group of bacterial protein toxins which, in the reduced state, lyse eukaryotic cells by disruption of the cytoplasmic membrane. Cell surface cholesterol is thought to be the target of the toxins. In the present work, the monolayer technique was used to investigate the interaction of four SH-activated toxins (streptolysin 0, alveolysin , perfringolysin 0, pneumolysin ) with various lipid films as a model for studying toxin-induced membrane disruption. A surface pressure increase up to very high values was elicited by reduced toxins (approximately equal to 10 nM) on films of cholesterol, other toxin-binding 3 beta-hydroxy-sterols, thiocholesterol and cholesterol-phosphatidylcholine mixtures suggesting deformation or penetration of the films. The surface-active potency of the toxins was of the same order as that of melittin and snake cardiotoxins at similar concentrations. No pressure increase was observed on films made of pure phosphatidylcholine, lanosterol and other sterols lacking the 3 beta-OH group. Optimal efficiency was at cholesterol/phosphatidylcholine molar ratio of 1 to 1. The critical pressures for toxin interaction with phosphatidylcholine and cholesterol monolayers were 25 mN X m-1 and 45 mN X m-1 respectively. Toxin interaction with phosphatidylcholine [14C]-cholesterol films did not modify monolayer radioactivity, indicating no cholesterol desorption. No pressure increase was elicited by toxins inactivated by SH-group reagents, heating or neutralization with antibody. Toxin effect was dependent temperature and pH. The overall potency of the four toxins tested was streptolysin 0 greater than alveolysin approximately equal to perfringolysin 0 greater than pneumolysin . The monolayer system mimicked in several respects toxin interaction with eukaryotic cells.