Multi-drug resistant bacteria spread in cystic fibrosis patients

Friday April 30th 2021

A multi-drug resistant bacteria has been shown to evolve and spread widely among cystic fibrosis patients.

University of Cambridge scientists behind a study published last night (29 April 2021) in Science say their findings demonstrate that patients with Mycobacterium abscessus infection must be treated immediately.

M. abscessus has become known as a significant threat to people with cystic fibrosis and other lung diseases because it can cause a severe pneumonia, leading to accelerated inflammatory damage to the lungs. Fewer than one in three cases is treated successfully.

The research team examined whole genome data for 1,173 clinical M. abscessus samples taken from 526 patients to study how the organism has evolved.

They found two key processes that play an important part in the organism’s evolution: horizontal gene transfer, where the bacteria pick up genes or sections of DNA from other bacteria in the environment, and within-host evolution.

Because of the shape of the lung, multiple versions of the bacteria can evolve in parallel, which is similar to what has also been seen in new SARS-CoV-2 variants in immunocompromised patients.

Professor Andres Floto, joint senior author from the Centre for AI in Medicine (CCAIM) and the Department of Medicine at the University of Cambridge and the Cambridge Centre for Lung Infection at Royal Papworth Hospital, said: “What you end up with is parallel evolution in different parts of an individual’s lung.

“This offers bacteria the opportunity for multiple rolls of the dice until they find the most successful mutations. The net result is a very effective way of generating adaptations to the host and increasing virulence.

“This suggests that you might need to treat the infection as soon as it is identified. At the moment, because the drugs can cause unpleasant side effects and have to be administered over a long period of time – often as long as 18 months – doctors usually wait to see if the bacteria cause illness before treating the infection. But what this does is give the bug plenty of time to evolve repeatedly, potentially making it more difficult to treat.”

The research team used mathematical models to track the organism’s evolution and compared samples from multiple patients to identify the key set of genes that enabled it to change into a potentially deadly pathogen.

They found the adaptations can occur quickly, but their ability to transmit between patients was constrained. However, the mutations that allowed the organism to become a more successful pathogen within the patient also reduced its ability to survive on external surfaces and in the air.

One important genetic change identified was one that contributed towards M. abscessus becoming resistant to nitric oxide and the team is to begin a clinical trial that aims to increase nitric oxide in patients’ lung by using inhaled acidified nitrite.

Professor Julian Parkhill, joint senior author from the Department of Veterinary Medicine at the University of Cambridge, added: “M. abscessus can be a very challenging infection to treat and can be very dangerous to people living with cystic fibrosis, but we hope insights from our research will help us reduce the risk of transmission, stop the bug evolving further, and potentially prevent the emergence of new pathogenic variants.”

The study was funded by the Wellcome Trust, Cystic Fibrosis Trust, NIHR Cambridge Biomedical Research Centre and The Botnar Foundation

Bryant, JM et al. Stepwise pathogenic evolution of Mycobacterium abscessus. Science 29 April 2021.

Tags: Genetics | Respiratory | UK News

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