Investigating the adjuvant activity of the proline-rich antimicrobial lipopeptide C12-PRP against antimicrobial-resistant veterinary bacterial isolates
Bibliographic record
Abstract
• A synthetic proline-rich lipopeptide, C 12 -PRP, was tested as an antibiotic adjuvant. • C 12 -PRP enhanced the efficacy of antibiotics against veterinary E. coli isolates. • The mode of action of C 12 -PRP likely involves outer membrane permeabilization. : Farm animals exposed to excessive amounts of antibiotics are reservoirs for antimicrobial-resistance genes and multidrug-resistant bacteria. The goal of this study was to investigate the adjuvant activity of a previously synthesized, proline-rich lipopeptide called C 12 -PRP in combination with various antibiotics against multidrug-resistant E. coli isolated from chicken and cattle. : The microbroth dilution method was used to determine the minimum inhibitory concentration of 10 antibiotics against four E. coli isolates. The adjuvant activity of C 12 -PRP was then tested in combination with the same antibiotics using a checkerboard assay. The best synergistic antibiotic-C 12 -PRP combinations were tested with the most resistant E. coli isolate using the Galleria mellonella insect infection model. A fluorescence-based membrane permeabilization assay was used to investigate a possible mode of action for C 12 -PRP. : The four E. coli isolates showed varying resistance to the antibiotics (0.008 µg/mL to ≥256 µg/mL), and overall, the addition of C 12 -PRP lowered the minimum inhibitory concentration. The two most-potent antibiotic-C 12 -PRP combinations were with novobiocin and erythromycin showing a susceptibility increase of 128-fold and up to 32–fold, respectively. G. mellonella survival was significantly improved when C 12 -PRP was included with novobiocin or erythromycin during treatment of infected larvae. Membrane permeabilization of an E. coli isolate was markedly higher in the presence of C 12 -PRP. : We demonstrated the synergistic ability of C 12 -PRP to enhance antibiotic activity and reduce the virulence of the veterinary E. coli isolates, strengthening the potential promise of this adjuvant candidate as a therapeutic agent for 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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".