New virus-antibiotic combination therapy fights antibiotic-resistant bacteria
An international team of scientists have found a novel way of treating antibiotic-resistant bacteria, making use of an ingenious combination of naturally-occurring viruses and medical antibiotics. The scientists from Université de Montpellier, France, and University of Pittsburgh, US, have successfully treated infections caused by the antibiotic-resistant bacteria Mycobacterium abscessus (M. abscessus) in genetically modified zebrafish using this method, and hope to extend treatment to human clinical trials after further experiments.
M. abscessus, a relative of the bacteria behind tuberculosis and leprosy, is responsible for particularly severe damage to human lungs and can be resistant to many standard antibiotics, making infections extremely challenging to treat. However, the bacteria are vulnerable to one unique bacteriophage – scientists have now identified and named it “Muddy,” a virus that can effectively destroy the M. abscessus bacteria.
Dr. Laurent Kremer, Université de Montpellier, and colleagues decided to test this new therapy in zebrafish, whose biology mimics how our immune system responds to bacterial infections. The zebrafish also carry a key genetic mutation for cystic fibrosis and are vulnerable to M. abscessus infections.
First, they needed to find out how these cystic fibrosis zebrafish reacted to the M. abscessus infection: monitoring the animals for 12 days, the scientists found that the fish developed serious infections with abscesses and suffered a high death rate; only 20% survived. Next the team tested how well the infected fish recovered when injected with Muddy over a period of 5 days. This time, the fish had much less severe infections, increased chances of survival (40%) and had fewer of the abscesses suffered by the fish during a severe infection.
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An antibiotic known as rifabutin was later found to be able to pair up with Muddy and could treat the M. abscessus infection as effectively as the bacteriophage alone. After identifying rifabutin, Dr. Kremer and colleagues treated the infected fish for 5 days with the antibiotic and bacteriophage. With this combination treatment, the fishes’ infections were much less severe; the fishes’ survival rate rocketed to 70% and they suffered far fewer abscesses. This is a dramatic improvement compared to fish treated with only the antibiotic, which had a 40% survival rate.
Having shown that it is possible to treat an antibiotic-resistant infection in zebrafish with specially targeted antibacterial bacteriophages, the scientists hope this treatment will eventually be transferred to the clinic to begin saving human lives.
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