Protein in the male reproductive tract is a potent anti-bacterial agent

Scientists at the University of North Carolina at Chapel Hill have found that a protein they discovered three years ago in the male reproductive tract is a potent anti-bacterial agent.

In addition to protecting the male against invading bacteria, the protein may aid fertilization by protecting sperm from harmful organisms encountered in the female reproductive tract.

A report of the study, now online, will be published in the July issue of the journal Endocrinology.

Designated DEFB118, the protein is found in the epididymis, a coiled duct through which sperm pass after leaving the testis. During passage through the epididymis, sperm become mature and acquire forward motility and fertilizing ability.

DEFB118 may be important in the innate immune system, said Dr. Susan H. Hall, associate professor of pediatrics in the UNC School of Medicine's Laboratories for Reproductive Biology.

"Antibodies for protection may not be present when a pathogen comes in, so we need an innate defense system, something right there and ready to go," Hall added.

A wide variety of anti-microbial proteins in different classes have been identified in species as diverse as insects and humans. The most abundant antibiotic proteins in humans are the defensins.

"This study demonstrates that the sperm-binding protein we discovered is an active defensin, one that has potent antibacterial activity," Hall said.

In humans, defensins are produced in the skin, eyes, nose, ears, mouth, digestive system, lungs and reproductive tract.

"When a pathogen tries to enter our bodies, defensins are ready and waiting there to kill them," Hall said. "And if the defensins are overpowered, then other protective mechanisms including antibodies are called in to finish the job."

Hall's laboratory first reported the new sperm-binding defensin, identified by graduate student Liu Qiang, in 2001. The protein may be a broad-spectrum anti-microbial that attacks and destroys a variety of bacteria, said UNC postdoctoral researcher Dr. Suresh Yenuga, the new report's lead author.

"This protein kills bacteria by disrupting their outer and inner cell membranes, resulting in the release of cell contents," he said. "In treating E. coli with different concentrations of DEFB118 over different time periods, we found it kills the bacteria within 15 minutes. Its anti-bacterial activity is dose-, time- and structure-dependent."

Study co-author and UNC postdoctoral researcher Dr. Yashwanth Radhakrishnan is exploring the evolutionary significance of defensin genes, how they evolved in the human genome. Numerous proteins similar in key attributes exist in different mammalian species, he said.

"We have already found homologues in monkeys, mouse and rat. The cluster of genes we're studying is 100 million years old," he said. "Do they have multiple functions or the same function? Are there differences in their mechanisms of action? Across species, we still have no data on function, or on what species of bacteria or viruses they kill. We hope to find some answers."

The Laboratories for Reproductive Biology, established more than 30 years ago, includes faculty in the departments of biochemistry and biophysics, cell and developmental biology, genetics, cell and molecular physiology, obstetrics and gynecology, and pediatrics. The LRB promotes understanding of normal and abnormal reproductive functions to discover new methods of treating infertility and develop new methods of fertility control.

LRB research is supported by grants from the National Institute of Child Health and Human Development, the NIH Fogarty International Center, the Contraceptive Research and Development Program, the Andrew W. Mellon Foundation and the Specialized Cooperative Centers Program in Reproduction Research at the NIH.

To view an image of the protein's effect on the bacteria, click on https://www.unc.edu/