Motility in the L3 stage is a poor phenotype for detecting and measuring resistance to avermectin/milbemycin drugs in gastrointestinal nematodes of livestock
| Autor: | Sue B. Howell, Lorraine Lopez-Soberal, Bob E. Storey, Melissa M. George, Ray M. Kaplan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Livestock Nematoda Movement 030231 tropical medicine Resistance Sheep Diseases Article Microbiology lcsh:Infectious and parasitic diseases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ivermectin parasitic diseases medicine Animals Pharmacology (medical) lcsh:RC109-216 Anthelmintic Doramectin Avermectin Pharmacology Anthelmintics Sheep biology Trichostrongyloidea Worminator Motility biology.organism_classification Drug Resistance Multiple Moxidectin Gastrointestinal Tract Milbemycin 030104 developmental biology Infectious Diseases Phenotype chemistry L3 Larva Abamectin Parasitology Haemonchus Macrolides Haemonchus contortus medicine.drug |
| Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance International Journal for Parasitology: Drugs and Drug Resistance, Vol 8, Iss 1, Pp 22-30 (2018) |
| ISSN: | 2211-3207 |
| Popis: | Motility is a commonly used in vitro phenotype for assessing anthelmintic activity of candidate compounds, and for detecting anthelmintic resistance in nematodes. Third-stage larvae (L3) of parasitic nematodes are commonly used in motility-based assays because L3 are simple to obtain and can remain viable in storage for extended periods. To improve the measurement of motility of microscopic stages of nematodes, our laboratory developed the Worminator, which quantitatively measures motility of parasites. Using the Worminator, we compared the dose-response characteristics of several avermectin/milbemycin (AM) compounds using L3 from both AM-susceptible and AM-resistant Cooperia spp. (abamectin, doramectin, eprinomectin, ivermectin, moxidectin) and Haemonchus contortus (eprinomectin, ivermectin, moxidectin). Concentrations tested with the Worminator ranged from 0.156 to 40 μM. Differences in EC50 between AM-susceptible and AM-resistant isolates of Cooperia spp. and Haemonchus contortus were small, with resistance ratios ranging from 1.00 to 1.34 for Cooperia spp., 0.99 to 1.65 for Haemonchus contortus. Larval migration inhibition assays were conducted using the same isolates and were equally ineffective for detection of resistance with resistance ratios less than 2.0. These results contrast with those of the Larval Development Assay where we obtained a resistance ratio of 16.48 using the same isolates of Haemonchus contortus. Moreover, even at the highest concentration tested (40 μM), 100% inhibition of motility was never achieved and EC50 for Worminator assays were more than 100× higher than peak plasma levels achieved in vivo following treatment. These data demonstrate that dose-response characteristics for inhibition of motility in L3 of gastrointestinal nematodes of livestock do not significantly differ for AM-susceptible and AM-resistant isolates. These data challenge the suitability of motility as a phenotype for detecting and measuring resistance to AM drugs in gastrointestinal nematodes of livestock. Graphical abstract Image 1 Highlights • Motility of L3 is a poor phenotype for detection of avermectin resistance. • Resistance ratios were less than 2.0 between susceptible and resistant isolates. • Confidence intervals overlapped between susceptible and resistant isolates. • Concentration to inhibit L3 motility is 100× peak plasma concentration in vivo. |
| Databáze: | OpenAIRE |
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