Raphael Hans Lwesya: fight antibiotic resistance with phages

Phages have been around for millennia, interacting with bacteria to establish a microbial equilibrium in the environment. Now, humans are calling upon phages as allies against antimicrobial-resistant infections that threaten the lives of millions. In this interview, I have had the honour of interviewing Raphael Hans Lwesya, MSc graduate from Makere University, about the potential of phage therapy to aid the fight against antibiotic resistance. He is also passionate about scientific communication, having founded The Phage to share the latest news in phage research and development. Read on to learn more about phages from one who has lived it throughout his career!

PN: Give us a birds-eye view of bacteriophages. What are phages, and what’s their life cycle like?

RHL: Bacteriophages, simply known as phages, are viruses that exclusively infect and replicate within bacteria. Phages are everywhere in nature, playing crucial roles in regulating bacterial populations and maintaining ecosystem balance. Phages are remarkable in that they have two major life cycles: the lytic cycle and the lysogenic cycle.

• Lytic cycle: In the lytic cycle, phages inject their genetic material into their host. The process hijacks the bacterial machinery away from replicating itself. Instead, the bacterial cells produce multiple copies of the infecting virus, eventually causing the cells to break apart in a process called lysis. When lysed, the bacterial cells release new phages ready to infect other bacteria and perpetuate the cycle.
• Lysogenic cycle: In the lysogenic cycle, something different happens after the phages inject their genetic material. Instead of hijacking the cells, phages integrate their genetic material into the host bacterium’s genome, becoming a dormant prophage. The prophage replicates alongside the host cell’s DNA and is then stably inherited during cell division. Interestingly, the prophage can switch to the lytic cycle under stress conditions or in response to environmental cues. After switching to the lytic cycle, active phage replication resumes and the host cell lyses.

A phage can exclusively infect and kill bacteria which make them promising candidates for treating infectious disease. Phages can target specific bacteria that cause disease, offering an alternative to traditional antibiotics for treating and managing diseases.

PN: We already have antibiotics to fight disease, so what’s driving the push for phages to treat infectious diseases? How would phages be administered?

RHL: Two developments in antibiotic research have raised the need for alternative strategies to combat infectious diseases. For the past few decades, we have seen a stark rise in antibiotic resistance. Combined with the limited arsenal of effective antibiotics, scientists have been eager to research the possibility of using phages to fight infectious diseases. Two traits of phages have encouraged scientists down this path:

• High specificity: Phages are remarkable in their ability to target and kill specific bacteria. When fighting disease-causing microbes, or pathogens, the specificity afforded by phages protects beneficial microbes from treatment. This selectivity reduces the risk of disrupting the body’s natural microbial balance, a phenomenon commonly seen with antibiotics. This specificity helps maintain your health during infectious disease therapy.
• Coevolution: Phages are living entities. Unlike antibiotics, phages can coevolve with their bacterial targets. As bacteria develop resistance mechanisms against phages, phages can also emerge with novel strategies to counteract resistance. An ongoing “arms race” between bacteria and phages emerges from this interaction, offering a dynamic and adaptable approach to combating bacterial infections.

Phages infect the target bacteria, replicate within them, and ultimately cause bacterial cell lysis. Within a period of time, phages can then help with eliminating microbial infections. Thus, phage therapy holds promise for treating a wide range of bacterial infections, especially when caused by multidrug-resistant microorganisms.

With the benefits of phage therapy clear, scientists have developed methods to isolate and use them to fight disease. First, researchers isolate and characterize phages that specifically target pathogenic bacteria. These phages are then formulated into phage cocktails, combining multiple phages into a single formulation to broaden the spectrum of bacteria they can eliminate. Clinicians can then administer the phage cocktails through various routes. These include topical applications, oral ingestion, or intravenous infusion depending on the specific infection site.

PN: On that note, what did you study for your Masters project? What new insights did you learn about phages through your research?

RHL: My Masters, entitled “Genomic characterization of bacteriophages for the development of cocktails for biocontrol of Aeromonas hydrophila,” focused on developing phage cocktails to combat infectious diseases. There, I focused on identifying and characterizing bacteriophages that could target Aeromonas hydrophila, a pathogen that infects aquatic organisms.

Through my research, I gained valuable insights into the genomic diversity and functional properties of these phages. By isolating and studying numerous phages, I discovered their remarkable ability to specifically target and lyse the pathogenic bacteria. Moreover, by analyzing their genomes, unraveling the genetic mechanisms behind their host recognition and infection strategies (I’m still learning more about phage genomics). This understanding paved the way for me to develop phage cocktails, combining multiple phages to enhance efficacy and overcome antibiotic resistance.

PN: That’s exciting! With you working on a phage cocktail yourself, where do you see the field of phage therapeutics going within the next 10 years?

The field of phage therapeutics is poised for significant advancements and widespread adoption within the next decade. Several key trends and developments suggest a promising future for phage-based interventions.

• Advances in phage biology: The body of phage research and clinical trials continues to grow, unravelling the complexities of phage biology. Through such research, we are enhancing our understanding of phage-host interactions and the factors that influence therapeutic efficacy. From there, we can design more effective phage cocktails to treat specific infections.
• Rapid phage characterization: We have also seen substantial advances in genomics and bioinformatics. Being able to sequence genomes at a high-throughput rate has allowed scientists to discover new phages and analyze their genomes. In doing so, we can streamline the process of phage selection and formulation to fight antimicrobial-resistant infections.
• Recognition of phage therapies: Regulatory agencies worldwide are beginning to recognize the potential of phage therapies to fight infectious diseases. With that recognition comes efforts to establish strong regulatory frameworks to use phages in the clinic. As we continue to accumulate safety and efficacy data, we can anticipate a more streamlined path to regulatory approval, paving the way for wider clinical adoption.
• Growing collaborations and networks: With the growth of phage research comes collaborations between researchers and industry stakeholders. Phage-based networks such as Phage Directory foster knowledge exchange, resource sharing, and accelerated progress in the field. This collaborative environment will help with developing standardized protocols, quality control measures, and robust manufacturing processes to produce phage-based therapeutics.

Overall, the next decade holds immense potential for phage therapeutics to become an integral part of the antimicrobial armamentarium, offering personalized and targeted treatments for bacterial infections.