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Cystic Fibrosis Trust

Whole genome sequencing of Mycobacterium abscessus

An investigation into how multi-drug resistant superbug Mycobacterium abscessus is spreading through the cystic fibrosis population and how best to prevent and treat it.

Key points

  • Using latest genetic sequencing technologies to understand how M. abscessus spreads.
  • World-class collaboration including Cambridge Institute for Medical Research, Cambridge Centre for Lung Infection and Wellcome Trust Sanger Institute.
  • Part of united global effort to enhance infection prevention/control, diagnosis and treatment.  

What is M. abscessus

Over recent years there has been a global increase in the number of serious infections in people with cystic fibrosis caused by non-tuberculous mycobacteria (NTM). The most common NTM to cause serious infection is the multi-drug resistant Mycobacterium abscessus, which is distantly related to tuberculosis and is usually found in the environment, particularly in water and soil. M. abscessus causes accelerated lung damage, is very difficult to treat and can make patients ineligible for lung transplant. We currently do not understand how individuals with cystic fibrosis acquire M. abscessus infection, how it can spread or how best to treat it. Recent research has found evidence that M. abscessus is a potential cross-infection risk for people with cystic fibrosis.

DNA graphicThere are many different mutations of M. abscessus and this, together with environmental data and social network analysis, makes it possible to track the way the bug spreads in a given population. Whole genome sequencing now makes it possible to identify the precise mutation or group of mutations in the M. abscessus present in each individual.

The research

The current study is being led by Dr Andres Floto, Consultant Physician at Papworth Hospital, with samples (or 'isolates') collected from a number of UK and international CF centres and analysed at Cambridge Institute for Medical Research (University of Cambridge) and Wellcome Trust Sanger Institute, the world leaders in human genomic research.

Dr Floto and his team previously sequenced the DNA code of almost 170 isolates of M. abscessus from individuals with cystic fibrosis, collected over a five-year period at Papworth Hospital, and proved that the bacteria can spread between patients, despite nationally recommended infection control measures being in place. The results were published in The Lancet on 29 March 2013. In response to The Lancet paper, the Cystic Fibrosis Trust established a working group to review national guidelines to protect people with cystic fibrosis from cross-infection risks from this type of multidrug-resistant bacteria. The Cystic Fibrosis Trust Mycobacterium abscessus Infection Control Working Group has produced interim guidelines and these are currently under consultation. A group representing the European Cystic Fibrosis Society and North American Cystic Fibrosis Foundation is currently developing guidelines on screening and treatment for NTM.

While the Lancet paper showed that person-to-person transmission took place at Papworth Hospital and there is a case report suggesting the same thing has happened at a CF centre in the US, the current study aims to establish whether this is happening more widely and should be treated as a systemic risk. The study is exploring whether the genetic makeup of the bacteria can predict the severity of the lung disease it causes and the type of antibiotics infected individuals will respond to. The whole genome sequencing of M. abscessus isolates from individuals with cystic fibrosis will also be used to understand the mechanisms of acquisition, to predict from the genetic code of their isolates how infected individuals will respond to specific treatment and to better understand how M. abscessus subverts the body's immune response which may suggest novel therapeutic strategies.

Dr Floto says: "This research is transforming our understanding of how M. abscessus causes infection and how we can most effectively treat it."

Dr Janet Allen, Director of Strategic Innovation at the Trust, says: "This grant is in line with the Trust's strategy to invest in research which will help alleviate and manage the symptoms of cystic fibrosis including more effective management of lung infections, particularly emerging infections such as NTM. The project also provides an excellent example of the kind of collaborative international approach we are keen to support going forward."

Dr Andres Floto is the Research Director of the Cambridge Centre for Lung Infection at Papworth Hospital and a Principal Investigator and Wellcome Trust Senior Clinical Fellow at the Cambridge Institute for Medical Research, University of Cambridge.

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