Naja naja atra and Naja nigricollis cardiotoxins induce fusion of Escherichia coli and Staphylococcus aureus membrane-mimicking liposomes

作者：Kao, Pei Hsiu; Lin, Shinne Ren; Hu, Wan Ping; Chang, Long Sen^*

来源：Toxicon, 2012, 60(3): 367-377.

DOI：10.1016/j.toxicon.2012.04.345

• Cardiotoxin
• Membrane-damaging activity
• Fusogenic activity
• Membrane-bound mode
• Membrane compositions

Our previous studies showed that the bactericidal effect of Naja naja atra cardiotoxin 3 (CTX3) and Naja nigricollis toxin gamma was associated with their membrane-damaging activity. To elucidate the mechanism responsible for CTX3- and toxin gamma-induced membrane permeability, we investigated the interacted mode of CTX3 and toxin gamma with model membrane of Escherichia coli (phosphatidylethanolamine (PE)/phosphatidylglycerol (PG), mol/mol, 75/25) and Staphylococcus aureus (PG/cardiolipin, mol/mol, 60/40) in this study. Membrane-damaging activity of toxin gamma on PE/PG and PG/cardiolipin vesicles were similar, while CTX3-induced leakage of PG/cardiolipin vesicles was notably higher than that of PE/PG vesicles. Noticeably, fusogenic activity of CTX3 and toxin gamma on the phospholipid vesicles correlated positively with their membrane-damaging activity. Unlike toxin gamma, CTX3 induced increasingly leakage and fusion of phospholipid vesicles with increased cardiolipin content. Changes in membrane fluidity and lipid packing occurred with the binding of CTX3 and toxin gamma with vesicles, reflecting the penetration of toxin molecules into membrane bilayers. Consistent with the finding that PE/PG and PG/cardiolipin vesicles induced differently conformational changes of CTX3 and toxin gamma. CTX3 and toxin gamma adopted different membrane bound-mode upon absorption onto either PE/PG or PG/cardiolipin vesicles. Taken together, our data indicate that membrane-bound mode and membrane-perturbing effect of CTX3 and toxin gamma in concert with targeted membrane compositions determine their fusogenicity and membrane-damaging activity, and suggest a causal relationship between bactericidal activity and fusogenicity of CTX3 and toxin gamma.

• 出版日期2012-9-1
• 单位中山大学