Recent research has reportedly shown a way to harness viruses in the fight against bacterial infection, reducing the threat of antibiotic resistance.
A growing number of infections, including pneumonia, tuberculosis, gonorrhoea, and salmonellosis, are developing antibiotic resistance, making them harder to treat and resulting in higher death rates, longer hospital stays and higher costs.
Phage therapy is the concept of using viruses (known as phage) that are harmless to humans to kill bacteria. It can be used in combination with antibiotics to cure infections more effectively, and reduce the opportunity for bacteria to develop antibiotic resistance. However, bacteria can also evolve resistance to phages.
The study at the University of Exeter, published in Cell Host Microbe, has illustrated a method combine antibiotics and phage therapy. Researchers conducted laboratory experiments on Pseudomonas aeruginosa, a bacterium which causes disease in immunocompromised and cystic fibrosis patients. They exposed the bacterium to eight types of antibiotics, finding differences in the mechanisms by which the bacteria evolve resistance to phages, which affect how harmful they are.
Viruses penetrate molecules on the cell surface to infect bacteria. Like the human immune system, bacteria have their own CRISPR defence system, made up of proteins that fight off infection. As in human immune responses, this means that the virus infects the bacteria, and is then killed. In the process, the bacteria’s CRISPR system learns to recognise and attack the virus in future.
Bacteria also have a second defence option. They can also change their own cell surface to ward off infection, losing the receptor to which phages normally attach. This option comes with a cost to bacteria - the bacteria become less virulent, meaning they no longer cause disease, or the disease becomes less severe.
In the study, four of the eight antibiotics tested caused a dramatic increase in the levels of CRISPR-based immunity. These antibiotics are all bacteriostatic – they do not directly kill cells but act by slowing down cell growth.
Professor Edze Westra, of the University of Exeter, said: “Antibiotic resistance is a major public health issue, and we need to take swift and urgent action. Phage therapy could be an important part of the toolkit, in reducing antibiotic use, and in using them in combination to increase their efficiency. We found that by changing the type of antibiotics that are used in combination with phage, we can manipulate how bacteria evolve phage resistance, increasing the chances that treatment is effective. These effects should be considered during phage-antibiotic combination therapy, given their important consequences for pathogen virulence.”
This research was funded through grants from the European Research Council under the European Union’s Horizon 2020 research and innovation programme.