Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study
Autor: | Martin G. Wagah, Marta F. Maia, Carlos Chaccour, Felix Hammann, Patricia Nicolas, Urs Duthaler, Caroline Kiuru, Martha Muturi |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Insecticides Mosquito Control Anopheles gambiae animal diseases Resistance Pharmacology chemistry.chemical_compound 0302 clinical medicine Ivermectin Cytochrome P-450 Enzyme System CYP Bioassay 610 Medicine & health biology Infectious Diseases Biological Assay Female Efflux ABC transporter Synergists medicine.drug Insecticide resistance 030231 tropical medicine Mosquito Vectors lcsh:Infectious and parasitic diseases Xenobiotics Lethal Dose 50 03 medical and health sciences Endectocide Detoxification Anopheles parasitic diseases medicine Animals lcsh:RC109-216 Research Cytochrome P450 biology.organism_classification Malaria 030104 developmental biology Parasitology chemistry biology.protein P-gp Xenobiotic |
Zdroj: | Nicolas, Patricia; Kiuru, Caroline; Wagah, Martin G; Muturi, Martha; Duthaler, Urs; Hammann, Felix; Maia, Marta; Chaccour, Carlos (2021). Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study. Parasites & Vectors, 14(1), p. 172. BioMed Central 10.1186/s13071-021-04675-9 Parasites & Vectors Parasites & Vectors, Vol 14, Iss 1, Pp 1-12 (2021) |
Popis: | Background Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively. Methods We determined the lethal concentration 50 for ivermectin in colonized Anopheles gambiae; then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification. Results Dual inhibition of xenobiotic pumps and cytochromes was found to have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin. Conclusion There is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin. Graphical Abstract |
Databáze: | OpenAIRE |
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