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
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine |
UniBE Contributor: |
Hammann, Felix |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1756-3305 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Tobias Tritschler |
Date Deposited: |
08 Jun 2021 15:33 |
Last Modified: |
05 Dec 2022 15:50 |
Publisher DOI: |
10.1186/s13071-021-04675-9 |
PubMed ID: |
33743783 |
Uncontrolled Keywords: |
ABC transporter Bioassay CYP Endectocide Insecticide resistance Ivermectin P-gp Resistance Synergists |
BORIS DOI: |
10.48350/155862 |
URI: |
https://boris.unibe.ch/id/eprint/155862 |
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