Effect of temporin A modifications on its cytotoxicity and antimicrobial activity

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Abstract:

Mäntylä T, Sirola H, Kansanen E, Korjamo T, Lankinen H, Lappalainen K, Välimaa AL, Harvima I, Närvänen A. Effect of temporin A modifications on its cytotoxicity and antimicrobial activity. APMIS 2005;113:497–505.

Temporin A (TA), a short α-helical antimicrobial peptide isolated from the skin of the frog Rana temporaria, is effective against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium strains. TA interacts directly with the cell membrane of the microorganism and it has been reported to be non-toxic to erythrocytes at concentrations that are antimicrobial. Less is known about the effects on the viability and growth of nucleated eukaryotic cells. In this study we have tested antibacterial and growth-inhibitory properties of TA, its dimeric analogue (TAd), and all-L (TAL L512) and all-D (TAD L512) enantiomeric derivatives of modified TA towards S. aureus and cultured human keratinocytes, respectively. All molecules were antibacterial at concentrations from 1.5 μM to 10 μM. In keratinocyte cultures, TAD L512, as well as TAd, showed cytotoxicity. The original TA and TAL L512 did not affect the viability of the cells at their bacteriolytic concentrations. The growth of keratinocytes in low- and high-calcium media was only slightly inhibited by temporins at concentrations which were antibacterial to S. aureus. This suggests that original TA and its modification, TAL L512, are promising molecules against multiresistant bacterial infections.

Keywords: Antimicrobial peptide; cytotoxicity; keratinocyte; temporin A

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2005.apm_107.x

Affiliations: 1: Department of Chemistry, 2: A. I. Virtanen Institute, University of Kuopio, Kuopio, 3: Peptide Laboratory, Haartman Institute, University of Helsinki, Helsinki, 4: Department of Dermatology, Kuopio University Hospital, Kuopio and 5: Institute of Applied Biotechnology, University of Kuopio, Kuopio, Finland

Publication date: August 1, 2005

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