Critical Role of P-Glycoprotein-9 in Ivermectin Tolerance in Nematodes
Bibliographic record
Abstract
Abstract Helminth infections in grazing ruminants are of major concern for animal welfare and cause substantial economic losses, prompting the widespread use of ivermectin (IVM). The emergence of IVM resistance, driven by complex and poorly understood mechanisms, increasingly compromises treatment efficacy. Drug efflux transporters, particularly P-glycoproteins (PGPs), are suspected to contribute to resistance. Yet, the study of their individual and functional role is hindered by their diversity in nematodes. This study aimed to dissect the role of specific PGPs in mediating IVM resistance. Thus, Caenorhabditis elegans strain IVR10, selected for IVM resistance and reported to overexpress pgp s, was used as a model. We generated different IVR10 strains each lacking one of six key pgp s, and assessed changes in IVM tolerance. Remarkably, only the deletion of pgp-9 significantly increased IVM susceptibility. Furthermore, transgenic expression of Haemonchus contortus pgp-9.1 rescued the resistant phenotype, demonstrating a conserved function across species. To explore drug dynamics, we developed a fluorescent IVM analog, which revealed reduced drug accumulation in IVR10, a phenotype reversed by pgp-9 deletion. Altogether, these findings show that nematode PGP-9 modulates IVM tolerance by controlling drug efflux and highlight it as a potential therapeutic target.
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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) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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".