New Discoveries Into Bacterial Growth In CF Patients’ Lung Infections

A new study on chronic lung infections associated with cystic fibrosis (CF) entitled “Polymorphonuclear Leukocytes Restrict Growth of Pseudomonas aeruginosa in the Lungs of Cystic Fibrosis Patients” recently published in the Infection and Immunity journal, is shedding new light on bacterial behavior in lung chronic infections and for the mechanism of interaction between the bacteria and the immune cells. The study was published by Kasper Nørskov Kragh, a Ph.D. a student of Prof. Thomas Bjarnsholt’s group at the Department of International Health, Immunology and Microbiology.

In this study, the research team transplanted infected tissue from lungs of cystic fibrosis patients without disturbing the bacterial cells and characterized the bacteria behavior and growth in these chronic infections. They show in the study that bacterial growth was blocked or decreased by immune cells through the consumption of oxygen, i.e. creating a hypoxic environment, therefore “suffocating” the bacteria and inducing it to change to a slower growth rate.

“The “suffocating” mechanism of the immune cells is the first time a bacteriostatic effect of immune cells has been described. The immune cells have up until now been thought to only kill bacteria, not halt their growth. In addition, this new insight helps us explain why the intensive and combinatory drug treatment approach developed and used in the CF clinic at Rigshospitalet, Copenhagen is as successful as it is,” said Prof. Bjarnsholt in the Faculty of Health and Medical Sciences press release.

This study brought light to the mechanism of bacterial growth and its interaction with the immune system of the host during lung chronic infection, which has not been very clear, and may contribute to the establishment a more adequate treatment with the use of specific antibiotic combinations, and may pave the way for the development of antibiotics targeting novel therapeutic candidates.

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“When we applied this to measure growth for bacteria living in biofilm in explanted lung tissue, we saw a diverse pattern of growth throughout our tissue sample. This puzzled us, and so we investigated possible correlations, and found that high local concentrations of immune cells restricted the growth of the bacteria. Furthermore in vitro experiments supported this mechanism of how the immune cells can remove oxygen and in this way vigorously restrict the bacterial growth,” added Kasper Nørskov Kragh.

“We show that it is possible to study the bacteria not only in shake flasks in the laboratory but directly in the very complex environment in an infection. This is a major improvement for chronic infections in general. On top of this, the new mechanism of the white blood cells is very important to understand chronic infections. It is fair to say that we are on the right track to understand chronic infections like cystic fibrosis and piece by piece we will solve the puzzle,” concluded Prof. Bjarnsholt.