Two University of Florida researchers report curing mice of the disease by using a virus to attack its bacterial source – Vibrio vulnificus. The scientists say the research may lead to techniques to purify oysters after harvest but before they reach raw bars and seafood markets – and might one day result in a better cure for the disease in people.
The work, reported in a November article in the journal Infection and Immunity, is part of a growing trend in research to use bacteria-attacking viruses, or "phages," to cure diseases caused by bacteria, said Paul Gulig, a UF professor of molecular genetics and microbiology at UF's College of Medicine. Although the disease caused by Vibrio responds to antibiotic treatment if caught early enough, the trend toward research of phages is spurred in part by the increasing ineffectiveness of antibiotics in killing ever-more-resistant bacteria, he and other researchers said.
"Phages haven't been used in the United States since the early 20th century because antibiotics have worked pretty well," he said. "That's changing now, and there is more interest in investigating the phage alternative."
Vibrio vulnificus is related to the cholera bacterium and occurs naturally in the presence of microscopic algae in seawater. When oysters eat the algae, Vibrio becomes concentrated. People can come into contact with the bacterium by eating raw oysters (cooking the bivalves kills the bacterium), or by exposing an open wound to water or mud where the bacterium is present.
Most exposed people suffer no ill effects because their bodies easily fight off the bacterium. However, people who suffer from liver damage – from alcohol-related cirrhosis, for example – may become infected. There are 30 to 50 cases of Vibrio vulnificus disease reported annually in the United States. Although rare, the disease is severe and often fatal, killing between 50 percent and 75 percent of those who are infected. The bacterium causes flu-like symptoms, followed by high fever, shock and half-dollar sized blood blisters mostly on the patient's legs.
Gulig and Donna Duckworth, a professor of molecular genetics and microbiology and co-author of the article, said because Vibrio resembles the flu or less-harmful diseases, it often remains undiagnosed until its later stages. At that point, the disease does not respond well to antibiotics, whence its high mortality rate, they said. Seeking an alternative to antibiotics, he and Duckworth decided to test the effectiveness of phages in attacking the disease.
The scientists isolated phages that prey naturally on the bacterium from oysters purchased from seafood markets and in mud collected from oyster beds in Florida's coastal waters. They grew the phages in the laboratory, then injected solutions containing concentrated amounts of the virus into the tail veins of mice infected with Vibrio. The result: The researchers found the phages cured the mice even well after they had begun experiencing symptoms of the disease.
"It was very clear that the phage treatment for many of the mice could completely protect them. It could prevent death, and it could essentially clear the mice of bacteria," Gulig said. "We showed that, in typical infections of mice, we get 100 million bacteria per gram of tissue, and in these treated mice we essentially could not detect any bacteria at all."
Gulig said the project didn't compare the phages with similarly timed antibiotic treatments, so the researchers couldn't say which is more effective. But phages have some tantalizing advantages over antibiotics, he said. While antibiotics naturally become diluted and leave the body after a period of time, phages grow and multiply until they have preyed on all the available bacteria, he said. Also, antibiotics are general treatments, killing harmful bacteria as well beneficial organisms, making patients vulnerable to yeast infections and other maladies. Phages, by contrast, are extremely specific, with the virus seeking only its natural prey and thus causing no unexpected outcomes.
The research was funded with a $64,000 grant from the U.S. Department of Commerce SeaGrant Program. The agency has awarded the scientists, in collaboration with Anita Wright, a UF assistant professor of food science and human nutrition, an additional $144,000 to pursue a new direction: using phages to purify oysters before they reach consumers. The idea would be to submerge the harvested oysters in vats of phage-treated water, allowing them to filter in the phage and kill off the Vibrio vulnificus before the oysters reach the market. Such technology would be quicker and cheaper to develop and commercialize than a new treatment for Vibrio disease, because it wouldn't have to meet regulatory standards for human medicine, Gulig said. "It would be a truly natural treatment, since we're essentially treating the oysters with something they're already exposed to in the wild," Gulig said.
Alexander Sulakvelidze, an assistant professor of microbiology and epidemiology at the University of Maryland, said the method appears promising.
"There are a number of approaches that allow you to clear oysters of Vibrio vulnificus, and none of them are optimal," Sulakvelidze said.
"They are very expensive or not very applicable for treating live oysters, so this may provide an additional tool to improve the safety of oysters."
Another goal of the UF research is to determine if phages can be used in a topical skin cream to help prevent contraction of Vibrio through skin wounds. "One thing we've thought about is having little vials of phage that fishermen can use prophylactically as soon as they get cut," Duckworth said.
ahoover@ufl.edu
Sources: Paul Gulig, Donna Duckworth
352-392-0050, 352-392-0681
gulig@ufl.edu, duckwort@mgm.ufl.edu
Journal
Infection and Immunity