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PLoS One ; 4(9): e7191, 2009 Sep 28.
Article in English | MEDLINE | ID: mdl-19784377

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Proteins/pharmacology , Animals , Antimicrobial Cationic Peptides , Circular Dichroism , Escherichia coli/metabolism , Female , Listeria monocytogenes/metabolism , Mice , Mice, Inbred BALB C , Peptides/chemistry , Rana temporaria , Salmonella enterica/metabolism , Staphylococcus aureus/metabolism
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