Sophisticated germ fighters found in alligator blood may help future soldiers in the field fend off infection, according to research by scientists at George Mason University. Their study (“Bioprospecting the American Alligator (Alligator mississippiensis) Host Defense Peptidome”), which appears in PLOS One, is the result of a fundamental research project supported by the Defense Threat Reduction Agency (DTRA) to find bacterial infection-defeating compounds in the blood of the crocodilian family of reptiles, which includes American alligators.
The project is about to start its fourth year and has received $6 million in funding to date from DTRA. If fully funded over five years, the project will be worth $7.57 million.
Alligators live in bacteria-filled environments and dine on carrion. Yet this ancient reptile rarely falls ill.
“After evaluation of the peptide sequences using a combination of rational and web-based bioinformatic analyses, forty-five potential antimicrobial peptides were identified, and eight of these peptides were selected to be chemically synthesized and evaluated,” wrote the investigators. “The successful identification of multiple novel peptides, exhibiting antibacterial properties, from Alligator mississippiensis plasma demonstrates the potential of this innovative discovery process in identifying potential new host defense peptides.”
“If you look at nature, sometimes we can find pre-selected molecules to study,” says study co-author Monique van Hoek, Ph.D. “I was surprised to find peptides that were as effective as they are in fighting bacteria. I was really impressed.”
Discoveries made by George Mason's 17-member, multidisciplinary research team could eventually find their way to the battlefield to protect warfighters from wound infections and potential exposure to biothreat agents. Researchers believe this work could benefit civilians too.
“We hope that these could be the basis to develop new treatments,” says Dr. van Hoek, a professor in the School of Systems Biology and the National Center for Biodefense and Infectious Diseases at Mason.
She and colleagues from the College of Science suspected the germ-fighting ability could be in the form of antimicrobial peptides. These small proteins are part of the innate immunity of alligators and even humans; all higher organisms make antimicrobial peptides.
“It's that part of your immune system that keeps you alive in the two or three weeks before you can make antibodies to a bacterial infection,” notes Dr. van Hoek. “It's part of your generalized immune response to the world. Innate immunity may work less well than antibodies, but it works well enough. “The reason why we're so interested in them: they are part of nature's way of dealing with the onslaught of bacteria and viruses that we face every day. Every breath that you take, everything that you eat, you're constantly exposed to bacteria and your body needs to fend them off in some way.”
Alligator blood samples were obtained from the University of Florida and the St. Augustine Alligator Farm Zoological Park.
Co-author Barney Bishop, Ph.D., says he was surprised at the sophistication and diversity of the alligator's germ-fighting peptides. These reptiles have evolved with a formidable defense against bacterial infections.
The Mason team took an innovative approach in its study of the alligator blood samples. Dr. Bishop developed custom-made nanoparticles to preferentially capture the peptides out of the very complex mixture of proteins and peptides in alligator plasma. This process revealed an unexpected result: the identified potent germ-fighting peptides were only fragments of larger “parent” proteins, according to Dr. Bishop, who's also a professor in the department of chemistry and biochemistry.
The custom-made particles used in this project significantly shortened the number of steps required to capture and identify peptides that were present in alligator blood plasma. And the team stresses that they have learned a thing or two along the way about these ancient reptiles.
“You stay away from the business end,” Dr. Bishop jokes.
