The best method of winning a war is to have more soldiers on the battlefield than the enemy. When the enemy is vaster, it can cause pillage and plunder. That's what happens with acne.
Good viruses known as P. acne phages that kill the acne-causing bacterium (Propionibacterium acnes) keep the bacteria in check. But the bacterium, a normal resident of the skin, increases substantially at puberty, outpacing the virus and often resulting in an inflammatory response that causes the red bumps of acne.
Now a team of researchers from the University of Pittsburgh and University of California, Los Angeles, has taken a major step in understanding the balance between the 11 viruses or "phages" that kill the bacteria, along with a better understanding of how acne occurs when that viral-bacterial balance goes awry.
The study, published in the current issue of mBio, the online open-access journal of the American Society for Microbiology, outlines new strategies to treat acne beyond the current regimen of antibiotics, which can fail because of the bacterium's growing resistance to the drugs. That situation highlights the need for better therapies.
"The fact that acne continues to be quite a significant problem is a good illustration of how poorly effective our arsenal is in dealing with it," said Graham Hatfull, professor of biological sciences at the University of Pittsburgh and an author of the study. "Resistance to antibiotics is one of the key problems, and from a clinical perspective there are few alternative solutions."
The study, he said, "provides a variety of directions to take" without any promises that new therapies "will bear fruit."
Potential therapies could include high concentrations of phage to kill off the proliferation of acne-causing bacterium during puberty, or enzymes that the viruses produce that kill the bacteria by breaking down their cell membranes.
"This work has given us very useful information about the diversity of that set of enzymes and helps pave the way for thinking about potential applications," said Hatfull, who holds a doctoral degree in molecular biology.
The skin around hair follicles creates a cozy environment for a small group of microbes including the viruses and acne-causing bacteria. The research group sequenced the viruses' genomes and found them to be, to its surprise, similar. The team had expected them to be as diverse as phages that control other bacterial disease.
The lack of diversity among the 11 viruses indicates they likely evolved within a bacterial community that also lacked diversity in sharp contrast to the vast numbers of different bacteria and their phages in environments such as soil or compost.
Hatfull said the acne-causing bacterium serves no beneficial function with its inflammatory response leading to acne.
Elizabeth Kutter, professor emeritus at Evergreen State College in Olympia, Wash., said the use of phage in the United States has been largely overlooked as a means to fight bacterial infections because domestic focus has been on antibiotics. Much of the research has occurred in the 20th century in Eastern Europe. Another problem has been concern about patent rights on phage treatments as drug companies try to protect their investment in the research and development of such drugs.
The study reveals the potential of phage as a treatment that she said also could prove profitable, once it is developed.
The bacteria neither develop resistance to phage nor destroy good bacteria, said Kutter, who also holds a doctoral degree. The study also reflects the advantages, not available five to 10 years ago, of using genome sequencing to understand all the properties of phages.