Living in a community provides protection from unfavourable external influences and improves the survival chances of each single individual. A pathogen of pneumonia, Pseudomonas aeruginosa, exploits this advantage. It produces a harmful biofilm in the lungs of patients with cystic fibrosis, causing chronic infections which permanently damage the lung tissue. A particularly resistant form of this pathogen is the small colony variant (CSV). Bacteria of this type coat themselves in an extremely thick matrix of a sticky polysaccharide compound, which enables strong adhesion of the biofilm to the surface of the lung.
The production of the polysaccharide compound is regulated by three proteins interacting in close cooperation with each other. As Urs Jenal’s team have been able to demonstrate for the first time, that mutations in these proteins lead to the development of strongly adhesive SCV bacteria. In altering single protein building blocks, the scientists disrupted the finely tuned interactions between the three proteins and thus activated the signalling pathway for the production of the sticky polysaccharide matrix.
In a second step, the researchers investigated whether such modifications contribute to the pneumonia pathogen’s life-long persistence in the lungs of patients with cystic fibrosis. To do this they isolated the SCV bacteria in samples from patients and examined their DNA."Our research group could find various mutations in the blueprint for the proteins. Amongst them, the same mutations that we had previously identified as causing activation." explained Jenal. "These genetic mutations contribute as a causing factor to the production of the stable bacterial biofilm of Pseudomonas aeruginosa."
In people who have cystic fibrosis, the pathogen of the SCV type can withstand challenges from the immune system and antibiotics better than normal bacteria. They are the source of the repeated new break-outs of pulmonary infections and ultimately the main cause of the fatal course of the disease. With their newly acquired knowledge, Jenal and his team would now like to develop new methods, to combat the pathogens effectively and thus prevent chronic lung infections.
MEDICA.de; Source: University of Basel