Every year, 12–15 children are born with cystic fibrosis in Denmark, and around 470 patients are currently (2012) living with the disorder. Cystic fibrosis is the most common hereditary, non-dominant disorder in Western Europe, and no fewer than 150,000 Danes—three per cent of the population—carry the hereditary predisposition. Around 100,000 people suffer from cystic fibrosis at global level.
The PhD project was carried out in partnership with Copenhagen University Hospital, where Consultant Helle Krogh Johansen, MD, and Professor Niels Høiby collected the material.
A tough strain of bacteria adapts its DNA to suit life in the lungs of cystic fibrosis patients. The bacterial genome has now been mapped, however, and this could lead to improved treatment in just a few years.
In order to draw more benefit from the haemoglobin from red blood cells, pathogenic bacteria have adapted at genetic level to life in the lungs of cystic fibrosis patients. This is one of the findings Rasmus Lykke Marvig arrived at through mapping bacterial genomes from a period of 38 years.
Without treatment, most cystic fibrosis patients would die within the first year of their lives, and even though patients can live with the condition for 45 years or more today on account of progress made in both diagnosis and treatment involving antimicrobial agents, they still suffer from serious consequential illnesses.
Cystic fibrosis is hereditary and distinguished by disruption to the glandular function in a range of organs, including the lungs. One of the effects of the condition is that the airways secrete abnormally tough mucus, resulting in patients typically developing chronic bacterial infections in their airways. Bacteria resistant to antimicrobial agents constitute a widespread problem in treatment of the illness.
The bacteria whose genomes Rasmus Lykke Marvig has mapped as a part of his PhD at DTU Systems Biology stem from Copenhagen University Hospital, where they were collected over a period of 38 years. The strain of bacteria is called Pseudomonas aeruginosa and the samples were taken from a total of 41 patients.
What makes them unique is that a large proportion of them stem from the same tough bacterial strain that has succeeded in spreading infection from one patient to another during the past 38 years. Therefore, the mapping of the genomes presents an evolutionary image which—taking into account the short life cycle of the bacteria— is equivalent to having mapped the evolution of the human genome from the time man evolved from the large ape to the present day.
“One of the surprising findings from my mapping work is that the bacteria have adapted to life in patients’ lungs by altering their hereditary material so that they can draw even more benefit from the haemoglobin in our red blood cells. In fact, it has reached the point where they are absolutely dependent on it. Moreover, they have succeeded in adapting to our use of antimicrobial agents by developing resistance to them—and resistant bacteria constitute an immense problem in the context of treatment,” explains Rasmus Lykke Marvig, who defended his PhD at DTU Systems Biology in January 2014.
The knowledge generated by the project is sure to prove indispensable to doctors working to develop the treatment methods of the future, and closely targeted input to starve the haemoglobin-dependent bacteria is one obvious option.
“It cost USD 3 billion and took almost ten years to map the first human genome, which was published in 2000. It is expected that in 2014, the same process can be completed in a week at the cost of around USD 1,000. This is amazing progress and has opened up all kinds of possibilities,” says Rasmus , who will continue analysing the findings from his PhD project in his postdoc work.
Employed by Copenhagen University Hospital, Rasmus continues to work with his old research group at the DTU Biosustain laboratories. And his work has far-reaching perspectives. For example, it may lead to more closely targeted treatment with antimicrobial agents rather than the more aggressive broad-spectrum treatment favoured today. This could be achieved by developing tests for specific genetic markers in the pathogenic bacteria.
“It’s not beyond the bounds of possibility that we could start using some of these techniques within the next two years,” says Rasmus Lykke Marvig.