Roadmap for Phage technologies

What are we trying to achieve and why? What is the problem we are trying to solve?

Using phages which have a direct effect killing bacteria/pathogens (lytic and lysogenic).

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

Suppress development of Phage resistance and enhancing susceptibility.
Select both the ‘best’ and most aggressive phages and use them in combination to ensure phages with good synergies are used.
Finding phages against which bacteria struggle to develop resistance.
Limits of their use (depending on environment – under agriculture conditions). e.g., stability, dosage.
Develop better strategies to manipulate lytic phages – although techniques exist for E. coli phages and others with good genetic systems -these are still slow.
Lytic phages may produce lots of LPS toxins (bad = proinflammatory).
Lytic phages maybe ok for acute phase treatments, phage cocktails needed to avoid resistance.

What approaches could/should be taken to address the research question?

Passage of lytic phage combinations in bacterial cultures.
Metagenomics analysis of phage effects on microbial diversity, richness, and stability.
Identify phages specific for surface virulence determinants.
Investigate phages that bind with the sex pili produced by antimicrobial resistance plasmids – the phage may select for resistance in the bacterium because they have lost the plasmid that produce the pili.

What else needs to be done before we can solve this need?

Understanding phage-pathogen ecology.
Establishing a better ecological and bioinformatic framework to inform isolation.
Better understanding the biology of the bacterium to identify areas the bacteria in question live and we can find more phages.
Establishing better informed strategies to isolate or choose relevant phages.
Determining the phageome (basic studies are needed to determine the diversity of phages).
Investigating phage-kinetics (how they are distributed) in the host (especially for systemic use), with various delivery systems.
Investigating evolution of phages and their targets.
Developing new methods for detection and quantification of lytic phages.
Investigating new ways of selecting sequences to be kept (positive as well as negative screens).

Existing knowledge including successes and failures