Teens struggling with skin-scarring acne may soon find relief from an unusual source.
Scientists have used genetic sequencing to identify 11 new viruses with the potential to kill the out-of-control bacteria that leads to intense breakouts. The findings add to an emerging body of research that indicates benign-to-human viruses living naturally in and on the body may also be used to go after bed sores, leprosy and drug-resistant staph infections.
“Acne could be a superb clinical context for making a test-case for treatments of other diseases,” said Graham Hatfull, a biologist at the University of Pittsburgh, who co-authored the study on acne published this month. “It’s a very attractive prospect.”
The research re-energizes a century-old treatment method that was abandoned with the rise of antibiotics during World War II. As germs have built up a resistance to those drugs in recent years, scientists are seeking alternatives and the virus strategy “is in vogue again,” said Vincent Fischetti, a biologist at Rockefeller University in New York who is one of the pioneers of the revived approach.
The study of the acne-fighting viruses, called bacteriophages or simply phages, was published in the September-October edition of mBio, the journal of the American Society for Microbiology.
In it, scientists found phages that live side-by-side with the P. acnes bacteria on the faces of people who don’t get bad acne, theorizing that the viruses somehow helped to keep it under control, said Laura Marinelli, the lead author and a postdoctoral fellow at the David Geffen School of Medicine at the University of California, Los Angeles. The single-celled P. acnes bacteria that resides in pores can grow out of control in an oily environment.
Once they identified the viruses, the scientists found the viruses had the ability to kill isolates of the bacteria in lab dishes, opening the possibility they may one day be the basis for effective treatments for the most common skin disorder in the U.S., with more than 40 million sufferers.
When the genomes were examined, the researchers learned the phages that preyed on acne bacteria were “strikingly” similar, Marinelli said in a telephone interview. That suggests a package of phages could be created to keep the skin bacteria from forming resistance to any one of them, she said.
The researchers also were able to identify an enzyme used by the viruses to break down the bacterial cell wall and escape, their death blow, Marinelli said. That enzyme could become the basis for a smear-on treatment.
Using genomic sequencing is a new wrinkle in the search for effective phages, she said, “For every bacterium out there, there are phages that can kill it. If we do want to develop these phages as therapies, we want their genomes.”
Viruses are about 100 times smaller than bacteria. They cause diseases from HIV to the common cold by breaking through a cell’s walls, hijacking its reproductive machinery to spread and, finally, killing the cell when it leaves. That’s what they do to all cells they invade; when those cells belong to unfriendly bacteria, viruses become humans’ allies.
Bacteriophages were separately discovered by Frederick Twort in the U.K. in 1915 and Felix d’Herelle in France in 1917. Research into using them to treat bacterial diseases such as cholera, though, was mostly abandoned after the advent of antibiotics in the 1940s.
Other research into the use of viruses to fight bacteria is somewhat further along, although all of it is in the earliest stages. Rockefeller’s Fischetti, for instance, earlier licensed findings on a virus that may work against infection by the Staphylococcus aureus bacteria to ContraFect Corp., a closely held Yonkers, New York-based biotechnology company where he is now a scientific adviser.
ContraFect is using a virus enzyme as a potential treatment for methicillin-resistant staph infections, or MRSA. The first round of clinical trials will start in January, Fischetti said in a telephone interview.
Phage International Inc., based in Danville, California, is using phages to treat diabetic foot ulcers and bed sores, including those that are drug-resistant. Its clinics are in Tbilisi, Georgia, and Tijuana, Mexico. The field will continue to expand, Fischetti said.
The research involving acne, which Fischetti wasn’t involved with, adds knowledge to the field, he said.
By using genetic analysis to identify several similar phages tied to P. acnes that could be combined in a single treatment, the study -- which Fischetti labeled “high profile” -- offers a way around bacteria’s ability to mutate and resist treatment, he said.
“Bacteria becomes resistant very quickly, so for these technologies to work, they need a cocktail” of viruses to work together, Fischetti said. “There is only one species of organism that causes acne so the potential of using one or two phages to control these organisms is probably pretty good.”
Bacteria and the viruses that reproduce in them co-evolved, Marinelli said. That means some bacteria will naturally be resistant to phages.
That’s all right in the case of P. acnes, because even people without acne have them on their skin, she said. Rather, the idea is simply to reduce the numbers of the bacteria. Also, as the bacteria evolve and change, so will the phages.
Marinelli and Hatfull previously worked on tools for manipulating viruses, so scientists can insert or knock out genes at will, Hatfull said.
That may mean scientists may one day be able to overcome bacterial resistance by changing the viruses in ways that mirror the mutations seen in the bacteria.
“Antibiotic resistance is a huge problem,” Marinelli said. “What I like about phages is that they’re not dead ends. If you get resistance, you can select for phages that overcome it.”