<i>Stenotrophomonas maltophilia</i> natural history and evolution in the airways of adults with cystic fibrosis
Bibliographic record
Abstract
ABSTRACT Stenotrophomonas maltophilia is an opportunistic pathogen infecting person with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of S. maltophilia infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of S. maltophilia in a large Canadian cohort of pwCF over a thirty-seven year period. S. maltophilia was recovered at least once in 25.5% of the cohort. Yearly isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing. Most pwCF were infected by unique strains, but serial infections with different strains, and strains shared between patients, were observed. In chronic carriage, longer time periods between positive collection dates increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with genetic diversity driven by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Instead, genomic analyses suggested common, indirect sources as their origins. Sixteen multi-mutated genes were identified as having a potential role in adaptation of S. maltophilia to CF, including in a regulator of an efflux pump and in an iron acquisition gene cluster. The information derived from a genomics-based understanding of the natural history of S. maltophilia infection within CF provides unique insight into its potential for in-host evolution. IMPORTANCE In this largest and longest single center study of S. maltophilia causing infections in persons with cystic fibrosis, we concluded that patient-to-patient infection transmission had not occurred. We determined that infection by a new S. maltophilia strain was more likely the longer the time between its recovery in sputum, suggesting infection by individual strains is generally short-lived. Amongst bacterial isolates belonging to the same clonal complex, isolates could be better differentiated by their gene content than mutations, suggesting gene gain/loss may contribute more to the genetic diversity of these strains than mutation. Infection by multiple strains, or a shared strain found in at least one other person, was not associated with progression to end-stage lung disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".