Leakage and lysis of lipid membranes induced by the lipopeptide surfactin

Abstract

Surfactin is a lipopeptide produced by Bacillus subtilis which possesses antimicrobial activity. We have studied the leakage and lysis of POPC vesicles induced by surfactin using calcein fluorescence de-quenching, isothermal titration calorimetry and 31 P solid state NMR. Membrane leakage starts at a surfactin-to-lipid ratio in the membrane, R b % 0.05, and an aqueous surfactin concentration of C S w % 2 lM. The transient, graded nature of leakage and the apparent coupling with surfactin translocation to the inner leaflet of the vesicles, suggests that this low-concentration effect is due to a bilayer-couple mechanism. Different permeabilization behaviour is found at R b % 0.15 and attributed to surfactin-rich clusters, which can induce leaks and stabilize them by covering their hydrophobic edges. Membrane lysis or solubilization to micellar structures starts at R b sat = 0.22 and C S w = 9 lM and is completed at R m sol = 0.43 and C S w = 11 lM. The membrane-water partition coefficient of surfactin is obtained as K = 2 · 10 4 M -1 . These data resolve inconsistencies in the literature and shed light on the variety of effects often referred to as detergent-like effects of antibiotic peptides on membranes. The results are compared with published parameters characterizing the hemolytic and antibacterial activity.

Effect of themicrobial lipopeptide on tumor cell lines: apoptosis induced by disturbing the fatty acid composition of cell membrane

“…In the present study, we therefore focused on the effects of surfactin on the cellular fatty acid composition of membranes to elucidate its apoptosis mechanisms. We hypothesized that lipopeptides exert their inhibitory effects by interaction with membrane or cellular fatty acids as lipopeptides can interact with membrane phospholipids and penetrate into the membrane in a concentration dependent relationship (Carrillo et al, 2003;Heerklotz and Seelig, 2007). Our experiments showed that the composition of cellular fatty acids was influenced by lipopeptides.…”

Poly-l-lysines and poly-l-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane

“…In case of the less often observed graded mechanism [39] only a well-defined amount of dyesolution is released from the vesicles. It is not known which mechanism PLL and PLA follow.…”

Review of surfactin chemical properties and the potential biomedical applications

“…At high concentrations, the detergent effect prevails and it results in the disruption of the membrane. The local surfactin-to-lipid ratio (R b ) within the membrane necessary to start the leakage is R b ~ 0.05 [28]. The permeabilizing activity of surfactin is thus stronger than that of detergents such as Triton.…”

“…Although there is only limited knowledge of the lipopeptide molecular mode of action, a few key properties have been described. A number of lipopeptides tend to aggregate into oligomers and micelles and can readily interact with the cytoplasmic membrane via their hydrophobic moieties [28,59]. Thus, these types of compounds with their unusual structures that act rapidly on membrane integrity rather than on other vital processes are a growing source of concern in modern medicine and might perhaps hold promise for the development of a new generation of antibiotics [60].…”