ABSTRACT
Currently, multidrug-resistant bacteria are rapidly increasing worldwide because of the misuse or overuse of antibiotics. In particular, few options exist for treating infections caused by long-persisting oxacillin-resistant strains and recently proliferating carbapenem-resistant strains. Therefore, alternative treatments are urgently needed. The antimicrobial peptide (AMP) Lycosin-II is a peptide consisting of 21 amino acids isolated from the venom of the spider Lycosa singoriensis. Lycosin-II showed strong antibacterial activity and biofilm inhibition effects against gram-positive and gram-negative bacteria including oxacillin-resistant Staphylococcus aureus (S. aureus) and meropenem-resistant Pseudomonas aeruginosa (P. aeruginosa) isolated from patients. In addition, Lycosin-II was not cytotoxic against human foreskin fibroblast Hs27 or hemolytic against sheep red blood cells at the concentration of which exerted antibacterial activity. The mechanism of action of Lycosin-II involves binding to lipoteichoic acid and lipopolysaccharide of gram-positive and gram-negative bacterial membranes, respectively, to destroy the bacterial membrane. Moreover, Lycosin-II showed anti-inflammatory effects by inhibiting the expression of pro-inflammatory cytokines that are increased during bacterial infection in Hs27 cells. These results suggest that Lycosin-II can serve as a therapeutic agent against infections with multidrug-resistant strains.
Subject(s)
Antimicrobial Peptides/chemistry , Biofilms/drug effects , Drug Resistance, Multiple, Bacterial/drug effects , Spider Venoms/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antimicrobial Peptides/pharmacology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Erythrocytes/drug effects , Fibroblasts/drug effects , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/pathogenicity , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/pathogenicity , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Phagocytosis/drug effects , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity , Sheep , Spider Venoms/pharmacology , Spiders/chemistryABSTRACT
Antibiotic resistance is an important issue affecting humans and livestock. Antimicrobial peptides are promising alternatives to antibiotics. In this study, the antimicrobial peptide Css54, isolated from the venom of C. suffuses, was found to exhibit antimicrobial activity against bacteria such as Listeria monocytogenes, Streptococcus suis, Campylobacter jejuni, and Salmonella typhimurium that cause zoonotic diseases. Moreover, the cytotoxicity and hemolytic activity of Css54 was lower than that of melittin isolated from bee venom. Circular dichroism assays showed that Css54 has an α-helix structure in an environment mimicking that of bacterial cell membranes. We examined the effect of Css54 on bacterial membranes using N-phenyl-1-naphthylamine, 3,3'-dipropylthiadicarbbocyanine iodides, SYTOX green, and propidium iodide. Our findings suggest that the Css54 peptide kills bacteria by disrupting the bacterial membrane. Moreover, Css54 exhibited antibiofilm activity against L. monocytogenes. Thus, Css54 may be useful as an alternative to antibiotics in humans and animal husbandry.
