Recent research progress into how bacteria adapt and evolve in chronic lung infections in cystic fibrosis patients could lead to the development of improved treatment strategies, according to a new review by the University of Liverpool in England. The manuscript, “Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections,” was published in the journal Trends in Microbiology.
Cystic fibrosis is a debilitating, genetically inherited disease characterized by defects in a transport protein (the cystic fibrosis transmembrane regulator) which results in sticky mucus, most notably in the respiratory tract. CF patients are susceptible to chronic lung infections, the predominant cause of morbidity and mortality associated with the disease. Cystic fibrosis affects more than 10,000 people in the United Kingdom alone.
P. aeruginosa is a multidrug-resistant pathogen that is recognized for its ubiquity and advanced antibiotic-resistance mechanisms, and is usually found in patients with cystic fibrosis. The ecological flexibility of P. aeruginosa can be attributed to its large genome, which contains a particularly high proportion of regulatory genes, as well as a large number of genes involved in the catabolism, transport, and efflux of organic compounds.
There has been some progress in cystic fibrosis with the development of aggressive early eradication therapies whereby treatment is initiated as soon as the pathogen is detected, which delays the onset of chronic infection. However, once a chronic infection is established by P. aeruginosa, it is seemingly impossible to eradicate.
The review, conducted in collaboration with the University of York in the U.K., highlights how population genomic studies have allowed a rapid progress in our understanding of how P. aeruginosa adapts and evolves in chronically infected cystic fibrosis patients.
“Currently we know that populations of P. aeruginosa that infect cystic fibrosis lungs harbor huge amounts of diversity, including variation in antibiotic resistance and secretion of toxins. This diversity is dynamic over time, making accurate diagnosis and treatment challenging,” Prof. Craig Winstanley, of the university’s Institute of Infection and Global Health, said in a news release. “Experimental work is now beginning to provide insights into what drives this evolution during infections, including the role of social interactions.”
The inherent spatial structure and spatial heterogeneity of selection in the cystic fibrosis lung appears to play a key role in driving P. aeruginosa diversification.
“Given the limited efficacy of current antibiotics, we now need to establish how this bacterial evolution and dynamic diversity affects patients, in order to design alternative treatment strategies,” Winstanley said. “One potential area of future work is to see whether the evolutionary trajectory of P. aeruginosa in cystic fibrosis lung infections could be manipulated to minimize symptoms and improve patient outcomes.”