Cystic fibrosis affects over 30,000 people in the United States. Cystic fibrosis is a multi-system genetic disorder which affects the digestive track, sinuses, lungs and even sweat glands of patients. It is associated with a protein called CTFR, which transports chloride across the cell membranes and creates chronic lung and sinus infections, as well as pancreas duct blockage in about 85 percent of patients. A new study has now isolated cystic fibrosis lung bacteria in different regions among cystic fibrosis patients which relates to nutritional requirements, treatment resistance and more.
The study, led by Peter Jorth from the University Of Washington School Of Medicine, involved sampling the left and right lungs from ten patients at the upper, middle and lower lobe airways. By applying RNA sequencing techniques, the research team was able to determine that the vast majority of bacterial that were present were P. aeuruginosa.
This bacteria exhibited varying phenotypes based on the region of the lung in which it was found. These phenotypes included resistance and virulence factors. For example, in about 40 percent of patients examined, the bacteria would be resistant to a certain antibiotic in the upper region, while those in the lower region were sensitive to it.
The team discovered after sequencing 96 different isolates from the three lung regions, that the bacteria was independently evolving in each region. They were able to note that bacteria clustered together based on the region from which they originated, a phenomenon known as genetic compartmentalization. By analyzing that data, they were able to analyze the diversity of P. aeruginosa in each patient.
Interestingly, the first patient had only 328 SNPs, while the second two patients had 3,169 and 1,653 SNPs, respectively. Patient one’s data showed that there were differences related to growth capacity, antibiotic tolerance, stress and virulence in those sub-populations obtained from lower and upper lobes. What this means is that regional communities of the bacteria with similar protein expressions see their diversification driven by isolation in different lung regions.
The study is an important step in our understanding of why it can be so difficult to treat patients with cystic fibrosis. Because the same bacteria in one region of the lung can have completely different characteristics than that in a different region, killing the infection in one area can actually bolster the same infection in another.
In addition, while one region may become clear of cystic fibrosis lung bacteria, it can open the door for resistant bacteria from another region to move in and create re-infection in the vulnerable areas. The next step in study could be to explore and develop treatments that can adapt to differing characteristics in similar bacteria.
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