Bridging the Gaps: Systems-level approaches to antimicrobial resistance
Bacteriophages driving evolution towards loss of drug resistance – broadening phage host range
Paul Barrow (Veterinary Medicine and Science), Jonathan Hirst (Chemistry), Richard Emes (Veterinary Medicine and Science) and Tania Dottorini (Veterinary Medicine and Science)
The issue
Bacteriophages are viruses that infect bacterium such as E. coli and they can be used to weaken and destroy bacteria. Bacteriophages are often specific to certain bacteria, for example, a bacteriophage might only infect and damage certain types of E. coli, and would not infect other types of E. coli or other bacteria such as Salmonella. Bacteriophages might be used in the fight against antimicrobial resistance as alternatives to antibiotics or a way of weakening the bacteria so that antibiotics are more effective.
The research
Bacteria often contain plasmids; these are small DNA molecules within a cell (separate from chromosomal DNA) and they can replicate independently. The genes carried on plasmids can provide bacteria with genetic advantages, such as resistance to antibiotics. If we are able to stop bacteria from transferring these genes to one another we can potentially slow the rate of resistance to antibiotics. Our researchers want to use bacteriophages to drive bacteria to evolve until they lose their AMR-resistant plasmids.
Our researchers also want to explore ways of extending the effect of some bacteriophage so that they are less host-specific (i.e. one type of bacteriophage can affect many types of bacteria). This might theoretically allow us to use bacteriophage to reduce antimicrobial resistance on a large scale.Researchers will be exploring the kinetics of plasmid loss from laboratory and field AMR E. coli and Salmonella strains and isolating and characterising specific bacteriophages for possible use, using their extensive expertise in areas such as structural bioinformatics.
The impact
Manipulating bacteria such as E. coli to facilitate losing their resistance genes could extend the life span of antibiotics. This could be additionally valuable if we were able to broaden the effect to many different types of bacteria. This is a truly novel area of research, which may allow us to prolong the life span of antibiotics. It is essential that we take novel action like this because bacteria are increasingly resistant to the antibiotics that we currently have available.
If you are interested in finding out more about this research or about Bridging the Gaps please be in contact with Harry Moriarty h.moriarty@nottingham.ac.uk in the first instance.