Contributions of β-lactamase substrate specificity and outer membrane permeability to the antibiotic sheltering of β-lactam-susceptible bacteria
Bibliographic record
Abstract
The use of β-lactam antibiotics is threatened by antibiotic resistant bacteria that produce β-lactamases. These enzymes not only protect the bacteria that produce them but also shelter other bacteria in the same environment that would otherwise be susceptible. While this phenomenon is of clinical significance, many of the factors that contribute to β-lactamase-mediated antibiotic sheltering have not been well-studied. We report the development of a luminescence assay to directly monitor the survival of β-lactam-susceptible bacteria in the presence of β-lactamase-producing bacteria and β-lactam antibiotics. This method provides a rapid and scalable means of quantifying antibiotic sheltering in mixed microbial populations. We applied this assay to investigate the contributions of several factors to sheltering, including the class of β-lactam, the substrate specificity of the β-lactamase, and the cell wall permeability of the β-lactamase-producing bacterium. Our results show that the extent of sheltering that occurs not only depends on the particular combination of β-lactam and β-lactamase, but is also greatly impacted by the ability of a β-lactamase to access its β-lactam substrates.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".