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Antimicrobial Agents and Chemotherapy, February 2004, p. 685-688, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.685-688.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Effects of Positively Selected Sequence Variations in Human and Macaca fascicularis ß-Defensins 2 on Antimicrobial Activity

Nikolinka Antcheva,1 Michele Boniotto,2 Igor Zelezetsky,1 Sabrina Pacor,3 Maria Vittoria Verga Falzacappa,2 Sergio Crovella,2 and Alessandro Tossi1*

Department of Biochemistry, Biophysics and Macromolecular Chemistry,1 Department of Reproduction and Development Sciences,2 Department of Biomedical Sciences, University of Trieste, I-34127 Trieste, Italy3

Received 18 June 2003/ Returned for modification 6 September 2003/ Accepted 9 November 2003

The evolution of orthologous genes coding for ß-defensin 2 (BD2) in primates has been subject to positive selection during the divergence of the platyrrhines from the catarrhines and of the Cercopithecidae from the Hylobatidae, great apes, and humans. Three peptides have been selected for a functional analysis of the effects of sequence variations on the direct antimicrobial activity: human BD2 (hBD2), Macaca fascicularis BD2 (mfaBD2), and a variant of the human peptide lacking Asp4, (-D)hBD2, which is characteristic only of the human/great ape peptides. hBD2 and mfaBD2 showed a significant difference in specificity, the former being more active towards Escherichia coli and the later towards Staphylococcus aureus and Candida albicans. Asp4 in the human peptide appears to be important, as (-D)hBD2 was less structured and had a markedly lower antimicrobial activity. The evolution of ß-defensin 2 in primates may thus have been driven, at least in part, by different environmental pressures so as to modulate antimicrobial activity.


* Corresponding author. Mailing address: Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy. Phone: 39 040 5583673. Fax: 39 040 5583691. E-mail: tossi{at}bbcm.units.it.


Antimicrobial Agents and Chemotherapy, February 2004, p. 685-688, Vol. 48, No. 2
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.2.685-688.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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