This Article Full Text Full Text (PDF) All Versions of this Article: 145/7/3165    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yenugu, S. Articles by Hall, S. H. Search for Related Content PubMed PubMed Citation Articles by Yenugu, S. Articles by Hall, S. H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene

The Androgen-Regulated Epididymal Sperm-Binding Protein, Human ß-Defensin 118 (DEFB118) (Formerly ESC42), Is an Antimicrobial ß-Defensin

Laboratories for Reproductive Biology, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599

Address all correspondence and requests for reprints to: Dr. Susan H. Hall, Laboratories for Reproductive Biology, CB 7500, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599-7500. E-mail: shh{at}med.unc.edu.

Spermatozoa bind a variety of proteins as they pass through the proximal regions of the epididymis, where they acquire forward motility and fertilizing ability. Recent evidence indicates that certain epididymis-specific secretory proteins that bind sperm have antibacterial activity and may function as part of the innate immune system. We reported earlier that ESC42, now designated human ß-defensin 118 (DEFB118), is a sperm-binding protein. In this study, we demonstrate that DEFB118 has potent antibacterial activity that is dose, time, and structure dependent. Incubation of Escherichia coli for 60 min with 10 µg/ml DEFB118 reduced bacterial survival to 20% of the control, and 25 µg/ml reduced survival to 5% of the control. DEFB118 concentrations of 50 and 100 µg/ml further reduced survival to less than 2 and 1%, respectively. A biphasic effect of salt concentration on the antibacterial activity of DEFB118 was observed. Reduction of disulfide bonds and alkylation of cysteines resulted in the complete loss of antibacterial activity. DEFB118 caused rapid permeabilization of both outer and inner membranes of E. coli and striking morphological alterations in the bacterial surfaces visible by scanning electron microscopy consistent with a membrane-disruptive mechanism of bacterial killing. In contrast, eukaryotic cell membranes were not permeabilized by DEFB118, as indicated by the rat erythrocyte hemolytic assay. Studies on DEFB118 inhibition of macromolecular synthesis and membrane permeability in E. coli were consistent with a primary effect at the cell membrane level. DEFB118 may contribute to epididymal innate immunity and protect the sperm against attack by microorganisms in the male and female reproductive tracts.

This article has been cited by other articles:

				J. Harder, R. Glaser, and J.-M. Schroder Review: Human antimicrobial proteins effectors of innate immunity Innate Immunity, December 1, 2007; 13(6): 317 - 338. [Abstract] [PDF]

				Y. Radhakrishnan, M. A. Fares, F. S. French, and S. H. Hall Comparative genomic analysis of a mammalian {beta}-defensin gene cluster Physiol Genomics, August 20, 2007; 30(3): 213 - 222. [Abstract] [Full Text] [PDF]

				M.A. Palladino, T.A. Johnson, R. Gupta, J.L. Chapman, and P. Ojha Members of the Toll-Like Receptor Family of Innate Immunity Pattern-Recognition Receptors Are Abundant in the Male Rat Reproductive Tract Biol Reprod, June 1, 2007; 76(6): 958 - 964. [Abstract] [Full Text] [PDF]

				D. Motzkus, S. Schulz-Maronde, A. Heitland, A. Schulz, W.-G. Forssmann, M. Jubner, and E. Maronde The novel {beta}-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo FASEB J, August 1, 2006; 20(10): 1701 - 1702. [Abstract] [Full Text] [PDF]

				R. Eckert, F. Qi, D. K. Yarbrough, J. He, M. H. Anderson, and W. Shi Adding Selectivity to Antimicrobial Peptides: Rational Design of a Multidomain Peptide against Pseudomonas spp. Antimicrob. Agents Chemother., April 1, 2006; 50(4): 1480 - 1488. [Abstract] [Full Text] [PDF]

				A. I. Yudin, S. E. Generao, T. L. Tollner, C. A. Treece, J. W. Overstreet, and G. N. Cherr Beta-Defensin 126 on the Cell Surface Protects Sperm from Immunorecognition and Binding of Anti-Sperm Antibodies Biol Reprod, December 1, 2005; 73(6): 1243 - 1252. [Abstract] [Full Text] [PDF]

				K. Zhang, R. Gao, H. Zhang, X. Cai, C. Shen, C. Wu, S. Zhao, and L. Yu Molecular Cloning and Characterization of Three Novel Lysozyme-Like Genes, Predominantly Expressed in the Male Reproductive System of Humans, Belonging to the C-Type Lysozyme/Alpha-Lactalbumin Family Biol Reprod, November 1, 2005; 73(5): 1064 - 1071. [Abstract] [Full Text] [PDF]

				A. A. Patil, Y. Cai, Y. Sang, F. Blecha, and G. Zhang Cross-species analysis of the mammalian {beta}-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract Physiol Genomics, September 21, 2005; 23(1): 5 - 17. [Abstract] [Full Text] [PDF]

				S. Yenugu, R. T. Richardson, P. Sivashanmugam, Z. Wang, M. G. O'Rand, F. S. French, and S. H. Hall Antimicrobial Activity of Human EPPIN, an Androgen-Regulated, Sperm-Bound Protein with a Whey Acidic Protein Motif Biol Reprod, November 1, 2004; 71(5): 1484 - 1490. [Abstract] [Full Text] [PDF]