Can Phage Therapy be the solution to antibiotic resistance?

When Alexander Fleming accidentally discovered that fungal spore contamination killed off the bacteria growing on his petri dishes in 1928, it started off the era of antibiotics. Further research led to discoveries of New antibiotics in the 1960s and 70s as the “golden age of antibiotics.” Suddenly, no bacterial infection seemed untreatable. Everything including cancer treatment, dialysis, organ transplants and surgeries today require antibiotics. They are an irreplaceable component of modern medicine. [2]

The 2019 CDC Report on antibiotic resistance lists five urgent threats, two new threats and three threats on the watch lists. It highlights the urgency to address new antibiotic resistance mechanisms. The literature shows evidence of horizontal gene transfer between strains of unrelated species to create new Multidrug Resistant (MDR) infections. Millions of Americans now have an antibiotic resistant infection resulting from unnecessary use of antibiotics and bad stewardship in hospitals and care centers, overuse of common antibiotics in animal feed for American agriculture and exposure in daily life. The question is not if but when MDR infections can become widespread and overwhelm our antibiotic treatment regimens.

What can be done in the face of the prospect of a threat only getting worse overtime? One novel solution is bacteriophages, or viruses who prey exclusively on bacteria. These viruses are around three billion years old, killing off bacteria wherever they exist. They have been in an evolutionary arms race for billions of years with their bacterial hosts, playing an important role in keeping bacterial populations under control. Phages work by infecting cells by binding to the cell surface, injecting their DNA or RNA genome into the cell, and producing copies of themselves. After the cell is filled with new phages, the viruses break open the cell with lytic enzymes and spread to infect further bacteria. Thus far, phage therapy has been in development for diverse strains, including Salmonella, Mycobacterium Tuberculosis, E. coli, and Acinetobacter baumannii, among others.

Although harmless to us, they can kill off bacteria very quickly. In 1919, French-Canadian microbiologist Félix d’Herelle first discovered and experimented with bacteriophages and thought up phage therapy as a possible treatment. The first time it was used in humans was on four children who recovered from dysentery. With the introduction of antibiotics and their ease of use and widespread success, phages were put on the backburner until the 1980s when phage display and other techniques were developed. These are now used as a technique to find successful molecules against pathogens. The leading centers have historically been in the former Soviet Union states and satellite states of Georgia and Poland.[5] But recently, UC San Diego’s School of Medicine opened up its first phage lab in June 2018 as the “first dedicated phage therapy center in North America, bringing innovative research and clinical practice to the field of medicine.” These labs believe that phage therapy may be a step forward in the struggle against bacterial infection.

All of these new centers have applied new microbiology techniques to emphasizing phage therapy development. Some of these developments have gotten the approval of the FDA and are going into early-stage clinical trials. Many applications involve biofilm and lysins as well live viruses in treatment. All of these possible options mean that MDRs might not be an untreatable phenomenon, whose subsequent could mean a dark end to the clinical miracles of antibiotics. But these techniques must be developed in concert with completely novel classes of antibiotics. Currently, The CDC reports antibiotic research makes up only 2% of current pharmaceutical research, with very few drugs coming out since 1980. 

There are also issues with the current phage therapy technology that must be overcome before it can become a safe, practical, and effective method of treating bacterial infection. First, the phages are difficult to isolate and prepare as a treatment solution. They require heavy doses and don’t always replicate as quickly as desired. Phages can lead to immune reactions despite being harmless. Phages must be specific and some don’t work on every strain of a certain bacterial infection. They can only target bacteria which have certain surface antigens that are not present in every specimen. Many bacteria can build immunity to phages just like antibiotics by simply becoming unrecognizable through mutations to their surface antigens.

Nonetheless, phages are a promising solution that can be strain-specific solutions to MDR infections. There are reasons why phages never became an equal to antibiotics and were more work than the effort was worth. New efforts should be made on antibiotic development. Perhaps billions of dollars should not be poured into phages with other antibiotic efforts producing more practical fruit. But phages are a potential solution and should not be dismissed as a scientific curiosity; nor should phages be considered an historic dead end in our efforts to eliminate infection. Maybe they don’t deserve special consideration. But they do deserve to be taken seriously.

Edited by: Shubhanjali Minhas

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