title: Membrane-damaging activity of Taiwan cobra cardiotoxin 3 is responsible for its bactericidal activity.
abstract: This study investigates the causal relationship between membrane-damaging activity and bactericidal activity of Naja naja atra (Taiwan cobra) cardiotoxin 3 (CTX3). CTX3 showed greater inhibitory activity for the growth of Staphylococcus aureus (Gram-positive bacteria) relative to that of Escherichia coli (Gram-negative bacteria). The CTX3 antibacterial activity is positively correlated with the increase in membrane permeability of bacterial cells. Morphological examination showed that CTX3 disrupted bacterial membrane integrity.CTX3 showed similar binding capability with lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and destabilization of LPS layer and inhibition of LTA biosynthesis on cell wall increased the CTX3 bactericidal effect on E. coli. and S. aureus, respectively. Compared with that of E. coli, CTX3 notably permeabilized model membrane of S. aureus. CTX3 membrane-damaging activity was inhibited by LPS and LTA, while increasing the CTX3 concentration counteracted the inhibitory action of LPS and LTA. Oxidation of Met residues on loop II of CTX3 simultaneously reduced the membrane-permeabilizing activity and bactericidal effect of CTX3. Taken together, our data indicate that CTX3 bactericidal activity depends highly on its ability to induce membrane permeability.
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Chen
authors.forename: Pei-Hsiu
authors.initials: PH
authors.lastname: Kao
authors.forename: Yaw-Syan
authors.initials: YS
authors.lastname: Fu
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004546:Elapid Venoms / Q000737:chemistry / Q000494:pharmacology*; D017815:Elapidae; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D013682:Teichoic Acids / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004546:Elapid Venoms; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C055953:cobra cytotoxin III; C009900:lipoteichoic acid