Trade-offs between receptor modification and fitness drive host-bacteriophage co-evolution leading to phage extinction or co-existence
Bibliographic record
Abstract
Parasite-host co-evolution results in population extinction or co-existence, yet the factors driving these distinct outcomes remain elusive. In this study, Salmonella strains were individually co-evolved with the lytic phage SF1 for 30 days, resulting in phage extinction or co-existence. We conducted a systematic investigation into the phenotypic and genetic dynamics of evolved host cells and phages to elucidate the evolutionary mechanisms. Throughout co-evolution, host cells displayed diverse phage resistance patterns: sensitivity, partial resistance, and complete resistance, to wild-type phage. Moreover, phage resistance strength showed a robust linear correlation with phage adsorption, suggesting that surface modification-mediated phage attachment predominates as the resistance mechanism in evolved bacterial populations. Additionally, bacterial isolates eliminating phages exhibited higher mutation rates and lower fitness costs in developing resistance compared to those leading to co-existence. Phage resistance genes were classified into two categories: key mutations, characterized by nonsense/frameshift mutations in rfaH-regulated rfb genes, leading to the removal of the receptor O-antigen; and secondary mutations, which involve less critical modifications, such as fimbrial synthesis and tRNA modification. The accumulation of secondary mutations resulted in partial and complete resistance, which could be overcome by evolved phages, whereas key mutations conferred undefeatable complete resistance by deleting receptors. In conclusion, higher key mutation frequencies with lower fitness costs promised strong resistance and eventual phage extinction, whereas deficiencies in fitness cost, mutation rate, and key mutation led to co-existence. Our findings reveal the distinct population dynamics and evolutionary trade-offs of phage resistance during co-evolution, thereby deepening our understanding of microbial interactions.
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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; both teacher heads agree on what is shown here.
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".