Hannah Pye, PhD and Evelien Adriaenssens, PhD explore the potential of phages in combating antimicrobial resistance and advancing health across human, animal, and environmental domains.
Recent research underscores the growing significance of bacteriophages (phages) in One Health, an integrated approach to human, animal, and environmental health. Phages, which target and kill bacteria, are being explored for their potential in biocontrol and as therapeutics for humans and animals. A review published in Essays in Biochemistry assessed the diversity of phages used in One Health applications over the past five years. The study revealed that 98% of phages employed in One Health belong to the class Caudoviricetes, compared to 85% of sequenced phages. Although, RNA phages, which are part of the realm Riboviria and could be valuable for environmental biocontrol and human therapy, are underrepresented, with only three identified applications to date. This indicates a lack of diversity in commercially used phages and those selected for therapeutic purposes.
Phages have significant potential to mitigate antimicrobial resistance, yet their underutilization represents a missed opportunity to leverage the full diversity of phages in nature. Achieving optimal health for all will require continued exploration of phage-host interactions and the environmental factors that influence phage efficacy.
In an email interview with Hannah Pye, PhD, postdoctoral research scientist and Evelien Adriaenssens, PhD, group leader at the Quadram Institute Bioscience, the experts discussed key challenges in expanding phage diversity for One Health applications were discussed. They highlighted the difficulties in isolating novel phages, with current isolation methods and biases limiting the commercial and therapeutic use of phages. Additionally, Pye and Adriaenssens addressed the underutilization of ssDNA and RNA phages, noting their potential in advancing phage therapy and environmental biocontrol. They emphasized the importance of research into phage genomics and alternative culture methods to address antimicrobial resistance and further One Health objectives. Their insights are below:
“Phages are typically isolated from common environments like water, wastewater and soil, limiting the diversity of those used in One Health applications. Expanding isolation efforts to underexplored environments could increase diversity, as phages are ubiquitous and can be found wherever suitable hosts exist. However, some phages have specific culture conditions that make laboratory isolation difficult, even though they are detectable in metagenomic datasets. Overcoming these challenges requires optimising growth conditions and developing new culturing techniques to propagate these phages.”
“The basic techniques used for phage isolation have changed very little in the last century. In part, this is because growing a lawn of bacteria and looking for a zone of lysis is a cheap and successful way of isolating phages against bacteria of interest. Using similar methods with similar bacteria across the world has biased the global phage collection towards a limited number of pathogens and phages that are easy to spot on a plate."
The diversity of phages used in One Health is limited, with a need to explore ssDNA and RNA phages for broader applications.
Current phage isolation methods are biased, leading to a restricted range of phages being selected for use in medicine and biocontrol.
Advancing research into phage genomics and alternative culturing techniques is essential to expand phage applications and combat antimicrobial resistance.
"Breaking it down, phage isolation is often biased by the bacterial hosts used, as phages can only be isolated in the presence of a suitable host. This results in a limited diversity of phages available for commercial and therapeutic applications. Our study found that 98% of phages used commercially for One Health belong to a single taxonomic class (Caudoviricetes), likely due to the similarity of bacterial strains used for isolation and the isolation methods. For commercialisation, it is also important that phages can be produced at high titres and therefore, a further bias is introduced in only selection those phages that grow well in production settings. In a therapeutic context, most phages are selected against priority pathogens due to rising antimicrobial resistance, leading to an arsenal of phages with very similar characteristics and host ranges. Additionally, careful consideration must be given to avoid overlap between phages used in therapy and those implemented for environmental biocontrol, as this could drive phage resistance and make human pathogens harder to treat.”
“We suggest that ssDNA and RNA phages should be investigated more for their potential for phage therapy and environmental biocontrol, particularly as they have simpler genomes which could be more amenable to genetic engineering and synthetic biology. Despite their abundance in nature, they remain underutilised due to biases in isolation and characterisation methods, as standard laboratory conditions are clearly best at isolating head-tailed dsDNA phages. Furthermore, most molecular microbiology techniques are optimised for dsDNA, making it more difficult to adapt methods for ssDNA or RNA phages. However, as research in this area expands, we anticipate increased commercial interest and technological advancements that could highlight the therapeutic and environmental potential of these phages.”
“Future research into phage genomics and alternative culture methods could significantly contribute to addressing antimicrobial resistance and advancing One Health goals. A large proportion of phage genomes consist of hypothetical proteins with unknown functions. Understanding the functions of these proteins could help engineer phages that are more efficacious, less prone to resistance, and capable of infecting multiple bacterial strains. Additionally, researching alternative culturing methods and sourcing phages from extreme and underexplored environments, where they have adapted to diverse conditions, could expand the phages available for use in human and veterinary medicine, and environmental biocontrol.”
To conclude, phages offer the potential for advancing One Health by addressing antimicrobial resistance and environmental biocontrol. Expanding phage diversity through improved isolation methods and research into alternative phages, such as ssDNA and RNA, is essential to utilize their therapeutic and biocontrol capabilities fully. Further research is needed to optimize techniques and broaden phage applications.
