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    Biophysical studies on the antimicrobial activity of linearized esculentin 2EM

    Year: 2020

    Journal: Biochim. Biophys. Acta-Biomembr., Volume 1862, FEB 1

    Authors: Malik, E; Phoenix, DA; Badiani, K; Snape, TJ; Harris, F; Singh, J; Morton, LHG; Dennison, SR

    Organizations: Shah Abdul Latif University, Pakistan via the Higher Education Commission, Pakistan

    Keywords: Linearized esculentin 2EM; alpha-Helical structure; Tilted peptide; Gram-positive bacteria; Phosphatidylglycerol and cardiolipin

    Linearized esculentin 2 EM (E2EM-lin) from the frog, Glandirana emeljanovi was highly active against Gram-positive bacteria (minimum lethal concentration <= 5.0 mu M) and strongly alpha-helical in the presence of lipid mimics of their membranes (> 55.0%). The N-terminal alpha-helical structure adopted by E2EM-lin showed the potential to form a membrane interactive, tilted peptide with an hydrophobicity gradient over residues 9 to 23. E2EM-lin inserted strongly into lipid mimics of membranes from Gram-positive bacteria (maximal surface pressure changes >= 5.5 mN m(-1)), inducing increased rigidity (C-s(-1) up arrow), thermodynamic instability (Delta G(mix) < 0 -> Delta G(mix) > 0) and high levels of lysis (> 50.0%). These effects appeared to be driven by the high anionic lipid content of membranes from Gram-positive bacteria; namely phosphatidylglycerol (PG) and cardiolipin (CL) species. The high levels of alpha-helicity (60.0%), interaction (maximal surface pressure change = 6.7 mN m(-1)) and lysis (66.0%) shown by E2EM-lin with PG species was a major driver in the ability of the peptide to lyse and kill Gram-positive bacteria. E2EM-lin also showed high levels of alpha-helicity (62.0%) with CL species but only low levels of interaction (maximal surface pressure change = 2.9 mN m(-1)) and lysis (21.0%) with the lipid. These combined data suggest that E2EM-lin has a specificity for killing Gram-positive bacteria that involves the formation of tilted structure and appears to be primarily driven by PG-mediated membranolysis. These structure/function relationships are used to help explain the pore forming process proposed to describe the membranolytic, antibacterial action of E2EM-lin.
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