Investigation of outer membrane porin OmpC mutation mediated relationship between Cefotaxime antibiotic resistance and T4 phage resistance in Escherichia coli
Bibliographic record
Abstract
Outer membrane porin C (OmpC) is a protein porin found on the outer membrane of Gram-negative bacteria. In Escherichia coli, OmpC allows entry of hydrophilic molecules in to the cell, including cefotaxime (CTX), a cephalosporin antibiotic. Previous research has shown that clinical isolates of multidrug resistant E. coli with mutations in OmpC have increased resistance to cefotaxime. Research has also shown OmpC as a necessary receptor for T4 bacteriophage entry. Due to their mutual dependence on OmpC for entry, we hypothesize that exposure to cefotaxime would select for OmpC mutations that also confer resistance to T4 phage in E. coli BW25113. To test this, we first used a minimum inhibitory concentration (MIC) assay to confirm that deletion of ompC increased E. coli resistance to cefotaxime. With validation of this phenotypic difference, we selected for strains that showed comparable antibiotic resistance to the knockout via sequential passaging of E. coli BW25113 in increasing cefotaxime concentrations. When we subjected these resistant cultures to T4 phage, we saw trends suggesting decreased and delayed lysis as predicted. To confirm that OmpC was indeed the target of selection, we sequenced the ompC gene from these double resistant isolates and found consistent insertion mutations in a number of the isolates. The insertion was predicted to encode an α-helical motif protruding into the channel. This paper addresses the relationship between antibiotics and bacteriophage, an under-researched area in clinical microbiology, and holds implications for how we approach antibiotic therapy and multidrug resistant bacteria.
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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 | 0.001 |
| Science and technology studies | 0.000 | 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) | 0.001 | 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 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".