Before antibiotics became a common treatment for infections, researchers considered using viruses that infect bacteria, called bacteriophages as a therapy. Now that antibiotic resistant bacteria are killing tens of thousands of people annually, and the pathogens are expected to become more widespread in coming years, researchers have been taking another look at whether bacteriophages can help us deal with the antibiotic resistance crisis.
Microbes are in a race for survival like other organisms, so they compete with one another. For every bacteria, there is probably a virus out there that could kill it. Researchers have now attempted to treat a dangerous bacteria with a bacteriophage-antibiotic combination.
Many mycobacteria cause serious illness. Mycobacterium abscessus, for example, is related to the germ that can seriously damage human lungs, causes tuberculosis and leprosy, and is often resistant to standard drugs, which makes the infections it causes difficult to treat. Cystic fibrosis (CF) patients are especially vulnerable to M. abscessus.
Researchers at the University of Pittsburgh had found a bacteriophage called Muddy that could kill bacteria growing in culture. Laurent Kremer and colleagues from Université de Montpellier worked with them to assess Muddy in a zebrafish model of CF that carried a CF-related mutation. They isolated M. abscessus from a CF patient, and exposed the zebrafish model to the bacteria.
First, they tested the effect of the bacterial infection. In zebrafish, M. abscessus caused abscesses in the fish and death; only 20 percent of the fish survived twelve days of infection. But when the fish model was treated with Muddy for five days, starting at 24 hours after they were infected with M. abscessus, the infections were less severe, there weren't as many abscesses and their survival rate increased to 40 percent.
When the researchers added an antibiotic to the mix, the fish improved even more. Rifabutin was identified as a drug that could effectively treat the infection, and when the infected fish were treated with both rifabutin and the bacteriophage from one to five days post-infection, the survival rate increased to 70 percent. They also had less severe symptoms. The findings have been reported in Disease Models & Mechanisms.
More work will be needed, but the researchers are hopeful that this research will eventually be useful in the clinic, and could save lives. “We need clinical trials, but there will be many other questions to be answered on our way there,” said Graham Hatfull of the University of Pittsburgh.