Synergistic antibacterial and anti-inflammatory activity of temporin A and modified temporin B in vivo.
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.
Department of Soil, Plant, Environment and Animal Production Sciences, University of Naples Federico II, School of Biotechnological Sciences, Napoli, Italy. capparel@unina.it
Rosanna
R
Capparelli
Alessandra
A
Romanelli
Marco
M
Iannaccone
Nunzia
N
Nocerino
Raffaella
R
Ripa
Soccorsa
S
Pensato
Carlo
C
Pedone
Domenico
D
Iannelli
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002942:Circular Dichroism; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D008089:Listeria monocytogenes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000494:pharmacology*; D011896:Rana temporaria; D019779:Salmonella enterica / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D011506:Proteins; C104501:temporin