Using the ‘fire to fight fire’ approach - touted as a potential breakthrough in the fight against diseases like cancer - may backfire by making infections more damaging, a new study has warned.
Researchers from University of Exeter in the UK have found that introducing ‘friendlier’ less-potent strains into a population of disease-causing microbes can lead to increased disease severity. The research shows that far from being a ‘silver bullet’ to weaken disease, the practice of introducing pacifist microbes into a host could make the aggressive pathogen stronger, which could hamper disease management.
Until now, introducing friendlier cousins, which do not cause severe disease, into a population of pathogens has been shown to reduce disease severity and damage to the infected host. It has been suggested that this approach could be an effective way of treating cancer and research so far has proved effective and promising.
For example, scientists have already produced encouraging results in the fight against Clostridium difficile infections that are so common in hospitals. However, the researchers tested this strategy using a plant pathogen and found the therapy could go dramatically wrong, with devastating consequences for the host plant.
They introduced a mixed population of the fungus that causes this disease into rice, where the mixture included an aggressive strain and a pacifist mutant. They expected that the overall disease severity would decrease because of the presence of the pacifist strain. However, they found the opposite. The rice plants succumbed to much more severe disease.
The research shows that the therapy can in some circumstances have the opposite effect, and that the way the pathogen will behave can be unpredictable, leading to more severe disease. It highlights the need for these new strategies to be carefully tested before they are used therapeutically. The scientists used cooperation theory and mathematical modelling to identify the reason for their surprising result.
They found that in some circumstances pacifists “helped” aggressive microbes to be more efficient in utilising resources obtained from the host. “Our study shows that a promising disease management strategy may not always be effective and indeed may have damaging unforeseen consequences,” said Ivana Gudelj, professor at University of Exeter. “We find that the mechanisms driving our unexpected findings when treating rice blast infection are pertinent for many diseases involving bacterial and fungal pathogens,” said Gudelj. The study was published in the journal eLife.