Abstract
The majority of snake venom phospholipases A2 (svPLA2s) are toxic and induce a wide spectrum of biological effects. They are cysteine-rich proteins that contain 119-134 amino acids and share similar structures and functions. About 50% of the residues are incorporated into α-helices, whereas only 10% are in β-sheets. Fourteen conserved cysteines form a network of seven disulfide bridges that stabilize the tertiary structure. They show a high degree of sequence and structural similarity, and are believed to have a common calcium- dependent catalytic mechanism. Additionally, svPLA2s display an array of biological actions that are either dependent or independent of catalysis. The PLA2s of mammalian origin also exert potent bactericidal activity by binding to anionic surfaces and enzymatic degradation of phospholipids in the target membranes, preferentially of Gram-positive species. The bactericidal activity against Gramnegatives by svPLA2 requires a synergistic action with bactericidal/permeability-increasing protein (BPI), but is equally dependent on enzymatic- based membrane degradation. Several hypotheses account for the bactericidal properties of svPLA2s, which include “fatal depolarization” of the bacterial membrane, creation of physical holes in the membrane, scrambling of normal distribution of lipids between the bilayer leaflets, and damage of critical intracellular targets after internalization of the peptide. The present review discusses several svPLA2s and derived peptides that exhibit strong bactericidal activity. The reports demonstrate that svPLA2-derived peptides have the potential to counteract microbial infections. In fact, the C-terminal cationic/hydrophobic segment (residues 115-129) of svPLA2s is bactericidal. Thus identification of the bactericidal sites in svPLA2s has potential for developing novel antimicrobials.
Keywords: Bactericidal activity, catalytic activity, gram-negative, gram-positive, lipopolysaccharide (LPS), phospholipases A2s (PLA2s)
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