The Role of Bacteriophages in Combating Superbugs

Over the past few decades, the global misuse and overuse of antibiotics have led to the emergence of superbugs, a critical component of the antibiotic resistance crisis. Superbugs are bacterial strains that have developed resistance against many types of antibiotics. Superbugs cause infections that are not easily treatable and spread incredibly quickly, particularly in healthcare settings such as hospitals. Thus, we urgently need novel, effective strategies to combat superbugs.

Bacteriophages have been highlighted as a potentially advantageous weapon in the fight against superbugs, owing to their ability to effectively treat antibiotic-resistant infections. As a result, biotechnology companies, including Fixed Phage, are committed to accelerating bacteriophage research to develop effective phage therapies that may help combat the antibiotic resistance crisis. In this article, we will delve into the role of bacteriophages in combating superbugs, and the associated challenges that need to be overcome. 

What are Bacteriophages?

Bacteriophages are abundant viruses that infect and kill certain species of bacteria with an incredibly high degree of specificity. There are many species of bacteriophage, each with a different host range. Bacteriophages can be lytic or lysogenic. 

The bacteriophage first infects a bacterial cell, injecting its genetic material. Lytic phages then hijack the host’s cellular replication machinery to replicate, eventually causing the host cell to rupture (or lyse), releasing the newly formed phages to infect neighbouring bacteria. Lysogenic phages integrate their genetic material into the host’s genome, forming a prophage which remains dormant until it is activated, initiating the lytic cycle. 

Bacteriophages have several advantages over traditional antibiotics which make them an enticing candidate for treating superbugs. First, they have a much lower propensity than antibiotics for driving resistance and can be personalised to the specific infection in the individual patient. They can be used alone or in combination with antibiotics, which may increase their efficacy in targeting antibiotic-resistant infections. Furthermore, phages are inherently non-toxic, and due to their high specificity, they can combat pathogenic bacteria while leaving beneficial bacteria, such as the gut microbiome, unscathed. 

Bacteriophage Therapy: The Science Behind It

Bacteriophage therapy is an emerging field that uses phages to combat bacterial infections, particularly those caused by antibiotic-resistant superbugs. The first step in phage therapy is the identification and selection of appropriate bacteriophages. This process requires detailed knowledge of the bacterial species causing the infection, as phages are highly specific, often targeting specific strains within a species. The bacterial sample from the patient can be tested against a phage library, where phages are stored and categorised based on their target, to find the right phage. Once the appropriate bacteriophage (or cocktail of phages) is identified, it can be administered to the patient. It then binds to the specific bacteria, leading to the destruction of the bacteria and the elimination of the infection.

​Overcoming Challenges in Bacteriophage Therapy 

Despite the potential of bacteriophage therapy for treating antibiotic-resistant infections and combating superbugs, several challenges remain to be overcome before bacteriophage therapy becomes a broadly adopted treatment strategy. There are three critical challenges currently being faced in the realm of bacteriophage research and therapy: 

• Limitations in bacteriophage research 

Phage research is incredibly challenging, and more research is required to identify and characterise novel phages, including the characterisation of their interaction with the microbiome and the mechanisms of bacterial resistance to phages. A potential strategy for evading resistance by using multiple bacteriophage strains as phage cocktails is currently being explored. 

• Lack of validated clinical data

Currently, the validated, appropriately controlled data demonstrating the safety and efficacy of bacteriophage therapy is limited. Designing clinical trials to test bacteriophages is complicated due to their high specificity requiring a more personalised approach and auto-dosing properties that render dose control complex.

• Regulatory challenges

The regulatory framework and approval process for bacteriophage therapy is complex, and currently, no phages have been licensed for medical use in the UK. However, unlicensed phages can be used where other treatment options have failed. There is currently a push to develop clearer guidelines for phage therapy approval.

Common Superbugs and the UK Perspective

Superbugs pose significant health challenges, particularly in healthcare environments. In the UK, Methicillin-resistant Staphylococcus aureus (MRSA) and Carbapenem-resistant Enterobacteriaceae (CRE) are among the most prevalent superbugs.

MRSA is a form of Staphylococcus aureus that is resistant to several commonly used antibiotics, including the penicillin class. Although it can live harmlessly on the skin, it can cause serious infections if it enters the bloodstream, particularly in patients with weakened immune systems. 

CRE infections, which mainly arise in hospitals, are caused by Enterobacteriaceae bacteria, a large family of Gram-negative bacteria, that become resistant to carbapenems, a class of broad-spectrum antibiotics. CRE infections do not usually affect healthy individuals but pose a risk to those with compromised immune systems. Some strains of CRE are resistant to all known treatments. 

Efforts are ongoing to track and control the spread of superbugs. Researchers have developed DNA photofits to identify drug-resistant superbug infections and track their spread. Furthermore, researchers are developing phage therapy to combat superbug infections. This approach is currently being used to treat people who are particularly vulnerable to infection, such as those with weakened immune systems, when other treatment options have been exhausted. 

Advancements and Future Prospects of Bacteriophage Therapy

Despite remaining in its infancy, advancements in bacteriophage therapy have shown remarkable promise, with ongoing research intensifying. The potential impact of phage therapy on the healthcare industry is significant, with the prospect of addressing the antibiotic resistance crisis that poses a severe threat to global health and treating patients with superbug infections that represent a growing cause of death globally. The future of bacteriophage therapy is promising, with increasing research and development initiatives. The experimental treatment has already been implemented in some instances, indicating a progressive trend towards mainstream acceptance and use in the healthcare industry. For example, phage therapy is being tested as a strategy to control superbugs in Belgium, where more than 100 people have been treated since 2019. Hopefully, other countries will soon follow suit. 

However, several challenges remain, and biotech companies are likely to play a significant role in the further development and widespread adoption of phage therapies. For example, Fixed Phage is currently part of an exciting collaborative effort to establish a new UK phage therapy infrastructure which is likely to pave the way for the broader adoption of phage therapy as an innovative solution to an urgent global health problem. 

Conclusion

Overall, bacteriophage therapy holds immense promise in tackling antibiotic-resistant superbugs. While advancements highlight a progressive shift towards its acceptance in healthcare, challenges such as bacteriophage resistance, limited clinical data, and regulatory complexities persist. Biotech companies such as Fixed Phage are instrumental in navigating these hurdles and fostering the broader adoption of phage therapy. As the magnitude of the antibiotic resistance crisis grows, the urgency to refine and implement bacteriophage-based strategies escalates. Furthering our understanding and application of these powerful viruses could ultimately revolutionise the fight against the dangerous spread of superbugs.