A new method of testing the most common cause of life-threatening infection in people with cystic fibrosis could improve efforts to study and combat the illness. The bacterium Pseudomonas aeruginosa is a leading contributor to hospitalizations, serious illness and early death for people with cystic fibrosis (CF). Scientists at The University of Texas have found a way to re-create conditions specific to the environment in which the bacterium spreads in the lungs of a person with CF, allowing them to identify several genes that appear to be necessary for its survival. The opensource study is published in the journal Proceedings of the National Academy of Sciences.
In cystic fibrosis, a serious genetic disease that causes recurring lung infections, bacteria colonize a patient’s lungs, usually beginning in childhood, leading to difficulty breathing. One of the most dangerous of these bacteria is P. aeruginosa, which, within the unique mucus that forms in the lungs of a person with cystic fibrosis, develops into large, antibiotic-resistant colonies. For the past decade, researchers have understood that Pseudomonas is arguably the major colonizing infection for people with cystic fibrosis.
Although scientists first mapped the genetic structure of P. aeruginosa 15 years ago, efforts to pinpoint how it behaves during an infection and which genes would need to be turned off to stop its spread have been hampered in part by the difficulty of mimicking the unique conditions of a cystic fibrosis patient’s lungs. Experiments that model the bacteria in animal cells, for example, have shown that P. aeruginosa behaves and grows in certain ways only when it is in the infected lungs of a person with CF.
In the current study the team applied new technology to bacteria thriving in actual samples of the mucus from CF lungs to model the behaviour of the bacterium in that environment. The team was then able to test tens of thousands of mutations of two strains of P. aeruginosa, which helped them identify key ways the pathogen behaves during an infection and the genes that might be essential for reproduction.
The team state that they have developed something other labs can replicate. Scientists at other institutions studying the bacterium and its effect on people with CF state that the research is important and indicated others will follow the lead of the current study. The new model allows the medical community to run large-scale experiments in conditions that are much more like the actual places where the bacteria colonize, without requiring researchers to collect countless specimens of actual mucus, called sputum, from humans.
Other institutions note that the ability to re-create conditions closer to the sputum in the lung of a CF patient will lead to better understanding of how different strains of the bacterium behave. It will also allow for easier identification of genes that contribute to the bacteria’s spread from patient to patient, and more meaningful scientific experiments to understand the bug’s resistance to antibiotics or identify new antimicrobial compounds that target specific genes necessary for maintaining these persistent infections.
The team summise that by re-creating the sputum that Pseudomonas grows in shows researchers which genes are important for bacterial fitness in this environment, opening the door to many new targets and therapeutic agents.