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Mapped bacterial genomes to improve CF patient treatment

Wednesday 19 Nov 14

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DTU Biosustain
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The results have been published in the prestigious scientific journal Nature Genetics.

The researchers behind the mapping project were Rasmus Lykke Marvig, Lea Mette Sommer, Søren Molin, and Helle Krogh Johansen.

Hardy bacteria strains adapt their genome to the lung environment in patients with long-term infections. Researchers from Rigshospitalet and DTU have mapped the genomes of over 500 bacteria to work out how.

A Danish research team from Rigshospitalet and DTU have mapped how bacteria adapt their genome to the lung environment in patients with long-term infections. The bacteria (Pseudomonas aeruginosa) samples were taken from 34 children and adolescents with the hereditary disorder cystic fibrosis (CF).

Analysis of the genomes of almost 500 bacteria found that there were 52 sections that were particularly important for the bacteria to change in order to survive in the patient. Many of these key areas were linked to antimicrobial resistance.

"It was found that the bacteria have adapted to life in the patient's lungs by changing their genome," reports Rasmus Lykke Marvig, postdoc at DTU Systems Biology and Rigshospitalet.

"It was found that the bacteria have adapted to life in the patient's lungs by changing their genome."
Rasmus Lykke Marvig, postdoc at DTU Systems Biology and Rigshospitalet

"This is how they become resistant to the antimicrobial agents doctors use in treatment. They have also changed their genome in many areas related to their surface structure, possibly indicating that the bacteria are attempting to avoid being recognized by the patient's immune system."

Mapping the bacteria genomes also showed that some patients were infected with the same hardy bacteria strain, which had passed from patient to patient. This is useful knowledge to guide efforts to develop future treatment methods, as the spread of resistant bacteria is a huge problem in relation to treatment.

This work may result in a more focused treatment with antimicrobial agents, rather than the more intense broad-spectrum treatment used today. One way it to develop tests for specific genetic markers in the pathogenic bacteria.

Cystic fibrosis

Every year, 12–15 children are born with cystic fibrosis in Denmark, and around 450 patients are currently living with the disorder.

Cystic fibrosis is the most common hereditary, recessive (both parents must be carriers) disorder in Western Europe, and 150,000 Danes—three per cent of the population—carry the hereditary predisposition. Around 100,000 people suffer from cystic fibrosis at a global level.

Without treatment, most cystic fibrosis patients would die within their first year. Patients can live with the condition for 45 years or more today due to progress in diagnosis and treatment using antimicrobial agents, but still suffer from serious secondary illnesses.

Cystic fibrosis is 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 an abnormally thick mucus, resulting in patients typically developing chronic bacterial infections in their airways. Bacterial resistance to antimicrobial agents constitutes a widespread problem in treatment of the illness.