Synergistic antibacterial and anti-inflammatory activity of temporin A and modified temporin B in vivo

• Published in: PloS one 2009-09, Vol.4 (9), p.e7191-e7191
• Main Authors: Capparelli, Rosanna, Romanelli, Alessandra, Iannaccone, Marco, Nocerino, Nunzia, Ripa, Raffaella, Pensato, Soccorsa, Pedone, Carlo, Iannelli, Domenico
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Animals; Anti-Bacterial Agents - pharmacology; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Antibacterial agents; Antibiotics; Antigens; Antimicrobial agents; Antimicrobial peptides; Bacteria; Bacterial infections; Biopolymers; Biotechnology/Applied Microbiology; Candida albicans; Chemistry; Circular Dichroism; Cytokines; Cytotoxicity; E coli; Escherichia coli; Escherichia coli - metabolism; Experimental infection; Female; Frogs; Gene expression; Glands; Gram-negative bacteria; Gram-positive bacteria; In vivo methods and tests; Infectious Diseases/Antimicrobials and Drug Resistance; Inflammation; Lethal dose; Listeria monocytogenes - metabolism; Membranes; Mice; Mice, Inbred BALB C; Peptides; Peptides - chemistry; Polypeptides; Proteins - pharmacology; Rana temporaria; Salmonella enterica - metabolism; Selaginella; Sepsis; Staphylococcus aureus - metabolism; Synergism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007191

Temporins are antimicrobial peptides secreted by the granular glands of the European red frog (Rana temporaria). They are 10-14 amino acid long polypeptides active prevalently against gram positive bacteria. This study shows that a synthetic temporin B analogue (TB-YK), acquires the capacity to act in synergism with temporin A and to exert antimicrobial and anti-inflammatory activity in vivo against gram positive and gram negative bacteria. Administration of 3.4 mg/Kg of temporin A (TA)+1.6 mg/Kg TB-YK, given to individual mice concurrently with a lethal dose of bacteria (gram positive or negative), rescued 100% of the animals. More importantly, the same doses of temporins, administered one week after experimental infection with a sub lethal dose of bacteria, sterilized 100% of the animals within 3-6 days. Also, it is described an animal model based on the use of sub lethal doses of bacteria, which closely mimics bacterial infection in humans. The model offers the possibility to test in a preclinical setting the true potential of TA and TB-YK in combination as antimicrobial and anti-inflammatory agents.