Bacteriophage therapy is making a crucial comeback this century as the emergence of antibiotic-resistant bacteria jeopardizes the efficacy of antibiotic treatments. Prior to the discovery of antibiotics, bacteriophages, or tiny viruses that kill bacteria, were commonly used to treat bacterial infections.
However, the century-old practice of using phage therapy was largely abandoned by the Western scientific community after the effective pioneering of antibiotics. Today, growing trends of antimicrobial resistance suggest that major health issues may resurface if possible methods are not explored.
“Because of the urgency of the problem, I think it’s important to look for alternative technologies,” Irene Chen, UC Santa Barbara Department of Chemistry and Biochemistry assistant professor, said. “One place to look for those alternatives is to go back to nature and ask: ‘What mechanisms exist in nature that control bacterial populations?’”
With an eye for creative impact, the National Institute of Health has awarded the Director’s New Innovator Award, a $2.1 million grant, to Chen to support her research on phage therapy.
Her research revisits this outdated virus treatment in recognition of its therapeutic potential and in hopes of revitalizing its utility.
It is the evolutionary arms race and the cusp of discovery, with scientists like Chen at the forefront of a new era of treatments.
For the past 70 years, the discovery and widespread use of antibiotics has saved countless lives and reduced critical health problems. However, resistance has eventually been seen in every antibiotic ever developed, as this was made possible by the ability to acquire/transfer genes, rapid bacterial division and quick evolution.
“Because they’ve evolved alongside antibiotics, bacteria have also evolved resistance mechanisms,” Chen said.
The rise of antibiotic resistance is attributed to a number of factors, including the overuse of antibiotics and the lack of new drug development by the pharmaceutical industry.
Although bacteriophages may not be a replacement for antibiotics, researchers like Chen are currently investigating their potential functionalities in targeting bacteria. Phage therapy works by infecting host cells with lytic bacteriophages to treat bacterial infections, and they have no adverse effects on human health.
A phage is composed of an inner core of nucleic acid wrapped in a protein coat; the basic features of a phage include a head (capsid) and a tail. A part of the protein capsule recognizes a distinct bacterial host, though the exact receptor that it binds to differs depending on the phage and the bacteria. Nature offers an unlimited supply of phages, and each strain is highly targeted to specific bacteria.
After the bacteriophage attaches itself to the host’s cell wall, the phage injects its DNA (or RNA) into the bacteria, usually passing nucleic acid through the hollow tail tube. The genetic information that gets transferred into the bacteria co-ops the machinery of the bacteria to potentially produce many more phages.
At this point, one of two cycles can occur: the lytic or the lysogenic cycle. The lytic cycle will allow for the rapid production of phages, resulting in lysis of the cell wall and infection of other bacterial cells.
During the lysogenic cycle, the phage’s DNA becomes integrated within the bacterial chromosome, combining to form a prophage. Once the bacterium reproduces, its daughter cells will carry potential phage production.
“We know that phages have been able to overcome bacterial resistance for billions of years. That they’ve survived and lived alongside bacteria for that long suggests that if the bacteria develop resistance to a particular phage we’re using, then we could hasten the evolution of the phage to overcome the bacterial resistance,” Chen said.
Chen’s current research focuses specifically on microbial sequencing to search for genes that may be useful in fighting bacterial infections. The system of interest is skin wounds, which allows her to directly apply a phage into a wound, like in a dressing or an ointment.
“Phages have a lot of potential advantages as a therapy over conventional antibiotics because you can imagine giving a relatively small dose, which will increase as they propagate on the host, and effectively produce a higher level than what you applied,” Chen said.
She hopes to find the presence of phages in wounds that heal to further pinpoint phage species. The next step would involve cloning those genes into a well-understood phage to make a hybrid phage for laboratory manipulation.
“There are definitely some important problems in our lifetime, like climate change, and I feel that antibiotic resistance is one in the medical field,” Chen said.
Chen and graduate student Samuel Verbanic will be working together on bacterial and microbial sequencing for the next five years in hopes of isolating genes, determining specific phages and discovering different phage delivery methods.
“The grant is for five years, but I definitely want this program to go on longer, so my hope is that my lab could continue this direction for decades because we want to get to that end goal, and that’s going to take some time.”