title: Naja naja atra and Naja nigricollis cardiotoxins induce fusion of Escherichia coli and Staphylococcus aureus membrane-mimicking liposomes.
abstract: Our previous studies showed that the bactericidal effect of Naja naja atra cardiotoxin 3 (CTX3) and Naja nigricollis toxin γ was associated with their membrane-damaging activity. To elucidate the mechanism responsible for CTX3- and toxin γ-induced membrane permeability, we investigated the interacted mode of CTX3 and toxin γ 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 γ 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 γ on the phospholipid vesicles correlated positively with their membrane-damaging activity. Unlike toxin γ, 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 γ 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 γ, CTX3 and toxin γ 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 γ 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 γ.
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, No 70, Lien-Hai Road, Kaohsiung 804, Taiwan.
authors.forename: Pei-Hsiu
authors.initials: PH
authors.lastname: Kao
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Hu
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry / Q000494:pharmacology*; D017815:Elapidae / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D008081:Liposomes; D008560:Membrane Fluidity / Q000187:drug effects; D008561:Membrane Fusion / Q000187:drug effects*; D008563:Membrane Lipids / Q000737:chemistry*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry; D011487:Protein Conformation; D016415:Sequence Alignment; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004179:Cobra Cardiotoxin Proteins; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; C082202:cardiotoxin III, Naja naja atra; C550831:toxin-gamma protein, Naja nigricollis