Researchers have found a virus that kills dormant bacteria, a discovery that could help to combat infections that can’t be treated with antibiotics.
For the first time, ETH Zurich researchers in Switzerland have isolated a bacteriophage from rotting plant material that can attack and kill bacteria in a dormant state.
Studies have shown that combination therapy with this phage and an antibiotic eradicates many dormant germs in pure culture and in a mouse model.
In nature, if bacteria experience nutrient deficiency or stress, they shut down their metabolism in a controlled manner and go into a resting state. In this stand-by mode, certain metabolic processes still take place that enable the microbes to perceive their environment and react to stimuli, but growth and division are suspended.
This also protects bacteria from antibiotics or bacteria-infecting viruses, phages. Until now, it was believed that phages successfully infect bacteria only when the latter are growing.
ETH Professor Alexander Harms and his team at the Biozentrum of the University of Basel discovered that bacteriophages that specialise in dormant bacteria do exist, though they are very rare.
How phages work still a mystery
In 2019, the team isolated a new, previously unknown virus that infects Pseudomonas aeruginosa, a bacterium that can cause serious respiratory diseases like pneumonia. They have named their new phage Paride.
The ETH researchers have not yet been able to clarify exactly how the phage works, but hope to elucidate the genes or molecules that underlie this mechanism, so that they can recreate it.
When tested in cell culture dishes, the virus was able to kill 99% of all dormant bacteria but left 1% alive. Only the combination of the Paride phages and antibiotic meropenem was able to eradicate the bacterial culture completely, even though the latter had no detectable effect on its own.
In a further experiment on mice with a chronic infection, the interaction between phages and antibiotics still proved to be very effective, though did not destroy the infection.
Studies by researchers at the Queen Astrid Military Hospital in Brussels showed that the treatment improved the condition of three-quarters of patients and that it was able to eliminate the bacteria in 61%.
“In the case of infections, that means it would be important to know the physiological state of the bacteria in question. Then the right phages, combined with antibiotics, could be used in a targeted manner. However, you need to know exactly how a phage attacks a bacterium before you can select the right phages for a particular treatment. This hasn’t happened yet because we still know too little about the phages,” Harms explained.