Mycobacterium abscessus, a cousin of tuberculosis and leprosy bacteria, causes particularly severe damage to human lungs and is resistant to many common medications, making infections extremely difficult to cure. There is, however, reason to be optimistic. Bacteria are susceptible to naturally occurring viruses known as bacteriophages; each bacteria species has its own bacteriophage that will kill it. To treat antibiotic-resistant infections, scientists are developing novel medicines that combine bacteriophages with the drugs we presently use. Laurent Kremer and colleagues from the Université de Montpellier in France and the University of Pittsburgh in the United States investigate the antibacterial effects of a new combination therapy that uses a bacteriophage and an antibiotic to treat infections caused by the antibiotic-resistant bacteria M. abscessus.
The Pittsburgh researchers had previously identified one bacteriophage out of 10,000, dubbed “Muddy,” that efficiently destroys bacteria in a petri dish and could be used to treat similar diseases in humans. The team, on the other hand, was looking for a different way to test their new medication than on patients. Kremer and colleagues decided to test their new combination therapy on zebrafish carrying the key genetic mutation that causes cystic fibrosis in humans and mimics how our immune system responds to bacterial infections, knowing that human cystic fibrosis patients are particularly vulnerable to M. abscessus infections. After that, the researchers received samples of an antibiotic-resistant strain of M. abscessus from a cystic fibrosis patient, which they used to infect cystic fibrosis zebrafish and test their new treatment.
They wanted to know how these cystic fibrosis zebrafish responded to the M. abscessus infection first. After 12 days of observation, they discovered that the fish had significant illnesses with abscesses and had a high mortality rate, with only 20% surviving. The researchers next examined how well the infected fish recovered after being injected with Muddy, an antibiotic bacteriophage, during a five-day period. This time, the fish had far fewer severe infections, had a 40% higher chance of survival, and had far less abscesses than after a severe infection.