This Article Full Text (PDF) Other Versions of this Article: AAC.01090-07v1 52/3/944    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tran, D. Articles by Selsted, M. E. Search for Related Content PubMed PubMed Citation Articles by Tran, D. Articles by Selsted, M. E.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.01090-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Microbicidal Properties and Cytocidal Selectivity of Rhesus Macaque Theta Defensins

Departments of Pathology & Laboratory Medicine, and Microbiology and Molecular Genetics School of Medicine, University of California, Irvine, CA 92697

^* To whom correspondence should be addressed. Email: meselste{at}uci.edu.

	Abstract

Rhesus macaque -defensins (RTDs) are unique macrocyclic antimicrobial peptides. The three RTDs (RTD1-3), isolated from macaque leukocytes, have broad spectrum antimicrobial activities in vitro, and share certain structural features with acyclic porcine protegrins, microbicidal peptides of the cathelicidin family. To understand the structural features that confer the respective cytocidal properties to -defensins and protegrins, we determined and compared the biological properties of RTD 1-3 and protegrin 1 (PG-1) in assays for antimicrobial activity, bacterial membrane permeabilization, and toxicity to human cells. RTD 1-3 and PG-1 had similar microbicidal potencies against Escherichia coli, Staphylococcus aureus, and Candida albicans in low ionic strength (10 mM) buffers at pH 7.4. The inclusion of physiologic sodium chloride partially inhibited -defensin microbicidal activities and the degree of inhibition depended on the buffer used in the assay. Similarly, inclusion of 10% normal human serum partially antagonized the bactericidal activities of all four peptides. In contrast, the microbicidal activities of PG-1 and RTD 1-3 against E. coli were unaffected by physiologic concentrations of calcium chloride and magnesium chloride. Treatment of E. coli ML-35 cells with RTD 1-3 or PG-1 rapidly rendered the bacteria permeable to o-nitrophenylgalactoside (ONPG), and this was accompanied by rapid entry of -defensin. Finally, although PG-1 was toxic to human fibroblasts and caused marked lysis of erythrocytes, -defensins were not cytotoxic or hemolytic. Thus, compared to PG-1, RTD 1-3 possess substantially greater cytocidal selectivity against microbes. Surprisingly, the low cytotoxicity of the -defensins did not depend on the peptides’ cyclic conformation.

This article has been cited by other articles:

• Lisanby, M. W., Swiecki, M. K., Dizon, B. L. P., Pflughoeft, K. J., Koehler, T. M., Kearney, J. F. (2008). Cathelicidin Administration Protects Mice from Bacillus anthracis Spore Challenge. J. Immunol. 181: 4989-5000 [Abstract] [Full Text]