23-Sep-2021 - The Company of Biologists

Ground-breaking bacteria-killing viruses unite with antibiotics to fight devastating antibiotic-resistant bacteria

Mycobacterium abscessus, a relative of the bacteria that cause 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, there is hope. Bacteria are vulnerable to naturally occurring viruses, called bacteriophages; for every species of bacteria, there is a unique bacteriophage that will destroy it. Scientists are testing new therapies that combine bacteriophages with the antibiotics that we currently use, to treat antibiotic-resistant infections. In their current Disease Models & Mechanisms article, Laurent Kremer and colleagues from Université de Montpellier, France, and University of Pittsburgh, USA, investigate the antibacterial effects of a new combination therapy, treating infections caused by the antibiotic-resistant bacteria M. abscessus with a bacteriophage and an antibiotic.

Previously, the Pittsburgh team had identified one bacteriophage out of 10,000, known as ‘Muddy’, that efficiently kills bacteria in a petri dish and could be a candidate for treating these infections in humans. However, the team wanted to find an alternative to testing their new therapy in patients. Knowing that human cystic fibrosis patients are particularly vulnerable to M. abscessus infections, 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. Then the team obtained samples of an antibiotic-resistant form of M. abscessus from a cystic fibrosis patient to infect the cystic fibrosis zebrafish and test their new treatment.

First, they needed to find out how these cystic fibrosis zebrafish reacted to the M. abscessus infection. Monitoring the animals for 12 days, they 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, the antibacterial bacteriophage, 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.

Then the authors searched for an antibiotic to pair up with Muddy and found that rifabutin could treat the M. abscessus infection as effectively as the bacteriophage alone. After identifying rifabutin, 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 vulnerable zebrafish with specially targeted bacteriophages, the authors hope this treatment can eventually be transferred to the clinic to begin saving human lives. “We need clinical trials, but there will be many other questions to be answered on our way there […] and zebrafish provide a very helpful tool for advancing these questions.” says Graham Hatfull from University of Pittsburgh, USA.  Matt Johansen (Université de Montpellier, France) is optimistic that zebrafish will continue to play a key role in our battle against antibiotic-resistance, saying “We believe that zebrafish will help us understand many bacteriophage-bacteria pairings in our fight against multi-drug resistant pathogens”.

Facts, background information, dossiers
More about Company of Biologists
More about Université Montpellier
  • News

    Hybrid material for controlled drug delivery

    A ladder-like aminopropylsilsesquioxane that could be used as a drug delivery system for ibuprofen has been synthesised by scientists in France.  The work demonstrates how it is possible to control drug delivery through the design and synthesis of a hybrid material. Drug release tests using ... more

More about University of Pittsburgh
  • News

    Bacterial lifestyle alters the evolution of antibiotic resistance

    How bacteria live -- whether as independent cells or in a communal biofilm -- determines how they evolve antibiotic resistance, which could lead to more personalized approaches to antimicrobial therapy and infection control. University of Pittsburgh School of Medicine researchers repeatedly ... more

    How CRISPR can help fight against neurodegenerative diseases

    Researchers of Sechenov University and University of Pittsburgh described the most promising strategies in applying genetic engineering for studying and treating Parkinson's disease. This method can help evaluate the role of various cellular processes in pathology progression, develop new d ... more

    Living longer or healthier?

    Aging research indicates that better healthspan--the quality of life as we age--may be more important than lifespan. In a report published in Nature Communications, a surprising new genetic discovery by researchers at the University of Pittsburgh School of Medicine and UPMC Children's Hospi ... more