Pseudomonas aeruginosa Prairie Epidemic Strain Population Dynamics and Evolution of Disease in Cystic Fibrosis Airways of Adult Patients
Bibliographic record
Abstract
The lower airways of patients with chronic airway diseases including cystic fibrosis (CF) are colonized by diverse communities of microorganisms. Over-time the airways of some 60% of CF patients become permanently colonized and dominated by Pseudomonas aeruginosa. Chronic infection of P. aeruginosa has been associated with a decline in pulmonary function, worse prognosis, and eventual patient mortality. Although P. aeruginosa evolves within the CF airways resulting in complex populations, the mechanism by which these complex populations contribute to disease progression is not well understood. Here we show diversity among isolates by observed changes in genome sequences of a strain of P. aeruginosa, known as Prairie Epidemic Strain (PES). Using whole genome sequencing and comparative genomics we identified a large core genome across 195 PES isolates from 57 CF patients of the Calgary Adult Cystic Fibrosis Clinic (CACFC) where 88% of the pangenome was categorized as core genes. Single nucleotide polymorphism (SNPs) mutations were shown to be the largest contributor of diversity at the nucleotide level compared to other polymorphism types consisting of 87% of the total polymorphisms present across the 195 PES isolates. CRISPR arrays and mobile elements such as prophage and plasmids demonstrate this strain of P. aeruginosa was stable over 30 years. In a second aim, I show variation in the populations of P. aeruginosa across an exacerbation event further highlighting the complexity of the lung bacterial community. Distinct populations of P. aeruginosa at the onset and resolution of an exacerbation within a single CF patient were identified by SNPs. These results a model where adaptive radiation as well as natural mutations contribute to the heterogeneity and diversification within populations of P. aeruginosa in CF patients. Understanding the evolution and population structure of PES through the identification of important genes and mutations through the clinical course of an exacerbation can aid in identifying new targets for patient treatment of P. aeruginosa in CF.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".