Use of Antimicrobial Peptides in Control of Mannheimia haemolytica that Cause Bovine Respiratory Disease
Bibliographic record
Abstract
Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. Upon arrival to the feedlot, cattle are often subject to metaphylactic treatment with macrolides to prevent bacterial cases of BRD, a practice that may promote antimicrobial resistance in BRD bacteria, impairing drug efficacy. Mannheimia haemolytica is one of the major bacterial causative agents of BRD. Emerging resistance to first line antibiotics has resulted in an urgent need for novel strategies to control members of the BRD bacterial complex. The inhibitory effect of two amphipathic, ?-helical (PRW4, WRL3) and one ?-sheet (WK2) antimicrobial peptides was evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. Isolates were also screened for biofilm forming ability using crystal violet staining. WK2 was determined to not be cytotoxic against bovine turbinate cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. The most robust biofilm former, Mh 330, was cocultured on bovine turbinate cells (BT) to assess the bactericidal activity of WK2. At 8-16 µg/mL, WK2 was bactericidal against Mh 330 in broth and at 32 µg/mL in the presence of BT cells, reducing the population by 3 logs CFU/mL without causing cytotoxic effects. To determine the inhibitory mechanism of the peptide, membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl ?-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides to control M. haemolytica as part of a BRD prevention and treatment strategies.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".