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Antimicrobial Agents and Chemotherapy, January 2008, p. 85-91, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00796-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Comparative Analysis of the Bactericidal Activities of Amphibian Peptide Analogues against Multidrug-Resistant Nosocomial Bacterial Strains{triangledown}

Maria Luisa Mangoni,2,{dagger} Giuseppantonio Maisetta,1,{dagger} Mariagrazia Di Luca,1 Ludovica Marcellini Hercolani Gaddi,2 Semih Esin,1 Walter Florio,1 Franca Lisa Brancatisano,1 Donatella Barra,2 Mario Campa,1 and Giovanna Batoni1*

Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università di Pisa, Pisa,1 Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche A. Rossi Fanelli, Sapienza Università di Roma, Rome, Italy2

Received 20 June 2007/ Returned for modification 21 August 2007/ Accepted 17 September 2007

Due to the widespread resistance of bacteria to the available drugs, the discovery of new classes of antibiotics is urgently needed, and naturally occurring antimicrobial peptides (AMPs) are considered promising candidates for future therapeutic use. Amphibian skin is one of the richest sources of such AMPs. In the present study we compared the in vitro bactericidal activities of five AMPs from three different species of anurans against multidrug-resistant clinical isolates belonging to species often involved in nosocomial infections (Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii). The peptides tested were temporins A, B, and G from Rana temporaria; the fragment from positions 1 to 18 of esculentin 1b [Esc(1-18)] from Rana esculenta; and bombinin H2 from Bombina variegata. When they were tested in buffer, all the peptides were bactericidal against all bacterial species tested (three strains of each species) at concentrations ranging from 0.5 to 48 µM, with only a few exceptions. The temporins were found to be more active against gram-positive bacteria, especially when they were assayed in human serum; Esc(1-18) showed fast and strong bactericidal activity, within 2 to 20 min, especially against the gram-negative species, which were killed by Esc(1-18) at concentrations ranging from 0.5 to 1 µM; bombinin H2 displayed similar bactericidal activity toward all isolates. Interestingly, while the activities of the temporins and bombinin H2 were almost completely inhibited in the presence of 20% human serum, the activity of Esc(1-18) against the gram-negative species was partially preserved in the presence of 40% serum. This property renders this peptide an attractive molecule for use in the development of new compounds for the treatment of infectious diseases.

* Corresponding author. Mailing address: Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università di Pisa, 56127 Pisa, Italy. Phone: 39-050-2213694. Fax: 39-050-2213711. E-mail: batoni{at}biomed.unipi.it

{triangledown} Published ahead of print on 22 October 2007.

{dagger} M.L.M. and G.M. contributed equally to this work.

Antimicrobial Agents and Chemotherapy, January 2008, p. 85-91, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00796-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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