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Cystic Fibrosis Sinus Infections Involve Microbes With Shifting Evolution Patterns

NEW YORK – The shifting nature of adaptation for Pseudomonas aeruginosa microbes found in the upper respiratory tract of cystic fibrosis patients with chronic rhinosinusitis may provide treatment clues that are not obvious from lung-centered microbial sampling, new research suggests.

"Our findings underscore the importance of infection-site biogeography to pathogen evolution and the relevance of the sinuses to overall CF respiratory health," co-senior and co-corresponding author Jennifer Bomberger, a microbiology and molecular genetics researcher at the University of Pittsburgh School of Medicine, and her colleagues wrote.

As they reported in a paper published in Cell Reports on Tuesday, the researchers used whole-genome sequencing, targeted 16S ribosomal RNA gene sequencing, "microbial identification after passive clarity technique" hybridization chain reaction (MiPACT-HCR)-based imaging, phenotyping, and other approaches to assess samples collected over time from half a dozen adult CF patients. Rather than analyzing lung sputum samples, they focused on less characterized P. aeruginosa communities in the upper respiratory tract, where early colonization occurs.

"Much of what we know about P. aeruginosa communities in cystic fibrosis is from sputum samples from the lungs," Bomberger explained in an email, noting that "our study is different in that we are analyzing P. aeruginosa evolution in the upper respiratory tract (i.e. sinuses)."

The team's results revealed distinct genomic features and adaptation events in the upper respiratory tract during different stages of infection and in relation to the size of the P. aeruginosa community considered.

Whereas early-stage infections involving large P. aeruginosa populations showed signs of selection related to the host environment and related treatments, leading to a rise in aggregation-prone bugs, later-stage infections tended to involve smaller, host-restricted population fragments that were prone to genome degradation and "mutator"-driven genetic drift effects.

"We propose that following initial adaptive evolution in larger populations under strong selection for aggregation, P. aeruginosa persists in small, fragmented populations that experience stronger effects of genetic drift," the authors reported.

The results hinted that MiPACT-HCR imaging or genome degradation signatures such as pseudogenization may help in distinguishing between P. aeruginosa populations in the process of selection and the genetic drift-prone populations found at later stages of the infection process.

Such differences in population size, structure, and evolutionary patterns may help in guiding therapeutic approaches, Bomberger noted, since P. aeruginosa populations with alterations that have arisen randomly through genetic drift are less likely to respond to targeted treatments, whereas populations under selection may be more amenable to therapeutic approaches targeting key mutations.

"This information would allow researchers and clinicians to know if the community is undergoing selection or more genetic drift and how likely mutations are to suggest selective pressures that could be effectively targeted therapeutically," she said.

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