The Developing World Urgently Needs Phages to Combat Pathogenic Bacteria

Bacteriophages are a sustainable alternative to control pathogenic bacteria in the post-antibiotic era. Despite promising reports, there are still obstacles to phage use, notably titer stability and transport-associated expenses for applications in food and agriculture. In this study, we have developed a lyophilization approach to maintain phage titers, ensure efficacy and reduce transport costs of Campylobacter bacteriophages. Lyophilization methods were adopted with various excipients to enhance stabilization in combination with packaging options for international transport. Lyophilization of Eucampyvirinae CP30A using tryptone formed a cake that limited processing titer reduction to 0.35 ± 0.09 log₁₀ PFU mL⁻¹. Transmission electron microscopy revealed the initial titer reduction was associated with capsid collapse of a subpopulation. Freeze-dried phages were generally stable under refrigerated vacuum conditions and showed no significant titer changes over 3 months incubation at 4 °C (p = 0.29). Reduced stability was observed for lyophilized phages that were incubated either at 30 °C under vacuum or at 4 °C at 70% or 90% relative humidity. Refrigerated international transport and rehydration of the cake resulted in a total phage titer reduction of 0.81 ± 0.44 log₁₀ PFU mL⁻¹. A significantly higher titer loss was observed for phages that were not refrigerated during transport (2.03 ± 0.32 log₁₀ PFU mL⁻¹). We propose that lyophilization offers a convenient method to preserve and transport Campylobacter phages, with minimal titer reduction after the drying process.

The antimicrobial resistance (AMR) crisis and HIV/AIDS epidemic exhibit many parallels. In both, infectious diseases have caused millions of deaths worldwide, with AMR expected to kill even more people each year than HIV/AIDS did at its peak. In addition, both have required or will require new classes of drugs for control. For HIV/AIDS, development of vital antiretroviral drugs (ARVs) was accomplished in several stages: expanding public awareness about the disease, gathering commitment from the international community to tackle the problem, and eventually establishing policies and global funds to deliver new therapeutics. For AMR, the pursuit of new antimicrobials appears to be following a similar trajectory. This paper examines how lessons and processes leading to ARVs might be applied to developing AMR drugs, in particular bacteriophages (phages). These possess many essential characteristics: inexpensive manufacture, rapid drug development, and a ready means to prevent phage-resistant microbes from emerging. However, the broad application of phage-based products has yet to be fully demonstrated, and will require both international coordination and modified regulatory policies.

There is growing interest in bacteriophage (phage) technologies across the One Health spectrum. The UK Parliament’s Science, Technology and Innovation Select Committee recently published the results of its inquiry into ‘the antimicrobial potential of bacteriophages’ with recommendations on clarity on regulatory matters to support research and innovation. Products developed for different sectors will have different regulatory requirements. Here, we discuss how phage technology is applied across human, veterinary and food sectors, highlighting key regulatory considerations and the technical challenges that must be addressed to assure the quality, safety and efficacy of phage products. We also highlight the potential impact of phages in areas where they are most needed (low- and middle-income countries).