Harnessing viruses to fight antibiotic resistance

 

Phage therapy is the concept of using viruses (known as phage) to kill bacteria, instead of using antibiotics. Until now, experiments have largely focussed on exposing bacteria to phage in a flask. Now, researchers have developed a new way to mimic these microenvironments, in which a single bacterium would colonize a specific area. Using this method, the team found that in these microenvironments Escherichia coli, a bacterium that is often responsible for food poisoning, does not become genetically resistant to phage, and the majority of the bacterial population is killed by phage.

 

Phage therapy is the concept of using viruses (known as phage) to kill bacteria, instead of using antibiotics. A growing number of infections, including pneumonia, tuberculosis, gonorrhoea, and salmonellosis, are becoming harder to treat, resulting in higher death rates, longer hospital stays and higher costs.

 

Bacteriophages (or phage for short) are viruses that kill bacteria. Unlike other viruses, they cannot harm humans and represent a promising alternative to antibiotics. Phage therapy was first used in 1919, when Parisian microbiologist Felix d'Herelle gave a phage cocktail to a 12-year-old boy, apparently curing his severe dysentery. Yet despite early promise, research dried up in the 40s as the world began to adopt the quick medical fix of antibiotics. Now, phage research is resurging as part of the solution to antibiotic resistance.

 

However, despite some remarkable case studies of phage therapy working in individuals, research has hit a number of obstacles. Among them is the challenge of recreating the way viruses behave in the body in lab environments.

 

Until now, experiments have largely focussed on exposing bacteria to phage in a flask. Here, the bacteria interact with each other and evolve swiftly -- their DNA changes and they too become resistant to phage, meaning any infection would persist. However, these flasks do not replicate how bacteria operate in organs such as the lungs, where they exist in "microenvironments" such as capillaries or air sacs known as alveoli.

 

Now, researchers at the University of Exeter have developed a new way to mimic these microenvironments, in which a single bacterium would colonise a specific area. Rather than mixing with lots of other bacteria, phage were introduced to each of these compartments in turn.

 

Using this method, the team found that in these microenvironments Escherichia coli, a bacterium that is often responsible for food poisoning, does not become genetically resistant to phage, and the majority of the bacterial population is killed by phage.

 

See:

 

Erin L. Attrill, Rory Claydon, Urszula Łapińska, Mario Recker, Sean Meaden, Aidan T. Brown, Edze R. Westra, Sarah V. Harding, Stefano Pagliara. Individual bacteria in structured environments rely on phenotypic resistance to phage. PLOS Biology, 2021; 19 (10): e3001406 DOI: 10.1371/journal.pbio.3001406

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)