Membrane sterol composition modulates the pore forming activity of syringomycin E in human red blood cells

The effect of lipopeptide antifungal agent, syringomycin E (SRE) on the membrane permeability of human red blood cells (RBCs) was studied. SRE added to RBCs above a concentration of 2x106 molecules/cell (50 microgram/ml RBCs) caused a rapid and concentration dependent lysis of a small subpopulation of RBCs; the extent of this lysis remained unchanged as long as 100 min. During this time period the membranes of the unlysed cells had enhanced permeability for ions which was monitored by direct measurement of 86Rb flux. Both the extent of cell lysis and ion transport rate showed linear relationships with SRE concentration demonstrating a random distribution of SRE molecules in red blood cells. The kinetics of the 86Rb efflux suggested pore formation by syringomycin E. The pores had discrete life times and were eventually inactivated. The pores were also a pathway for efflux of monomeric haemoglobin. Alteration of the membrane sterol composition, i.e. depletion of cholesterol by 50% or partial ergosterol substitution of the cholesterol increased the SRE induced membrane permeability for 86Rb by two orders compared to membranes with unaltered sterol composition. This modification of the sterol composition promotes the pore forming activity of this lipopeptide in the membrane.