Fitness cost of target-site and metabolic resistance to pyrethroids drives restoration of susceptibility in a highly resistant Anopheles gambiae population from Uganda

Tchouakui, Magellan, Oruni, Ambrose, Assatse, Tatiane, Manyaka, Claudine R., Tchoupo, Micareme, Kayondo, Jonathan and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2022) 'Fitness cost of target-site and metabolic resistance to pyrethroids drives restoration of susceptibility in a highly resistant Anopheles gambiae population from Uganda'. PLoS ONE, Vol 17, Issue 7, e0271347.

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Abstract

Background: Insecticide resistance threatens the effectiveness of malaria vector control, calling for an urgent need to design suitable resistance management strategies. Here, we established the resistance profiling of an Ugandan Anopheles gambiae population to insecticides using WHO procedures and assessed the potential restoration of susceptibility in the hybrid line Mayuge/KISUMU in an insecticide-free environment for eighteen (18) generations.

Results: This An gambiae population exhibited a very high intensity of resistance to permethrin, deltamethrin, and alphacypermethrin with a consistent loss of efficacy of all long-lasting insecticidal nets (LLINs) tested including PBO-based and new generation nets Interceptor G2 (IG2) and Royal guard. Molecular analysis revealed a fixation of the L1014S-kdr mutation together with the overexpression of some P450 metabolic genes (CYP6Z1, CYP9K1, CYP6P1, 3 & 4) besides the cuticular resistance-related genes (CYP4G16) and sensorial appendage proteins (SAP1, SAP2, and SAP3) but no GSTe2 overexpression. In the absence of selection pressure, the mortality rate after exposure to insecticides increased significantly over generations, and restoration of susceptibility was observed for most of the insecticides in less than 10 generations. Accordingly, a significant reduction in the frequency of KdrE was observed after 13 generations coupled with reduced expression of most metabolic resistance genes.

Conclusions: The results of this study show that the high intensity of pyrethroid resistance observed in An gambiae from Uganda associated with the loss of efficacy of LLINs could compromise vector control efforts. The study also highlights that an early rotation of insecticides could help manage resistance to insecticides by restoring the susceptibility. However, the persistence of Kdr mutation together with overexpression of some metabolic genes after many generations in the absence of selection pressure indicates the potential implication of modifiers alleviating the cost of resistance which needs to be further investigated.

Item Type:	Article
Subjects:	QX Parasitology > QX 20 Research (General) QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0271347
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	06 Oct 2022 08:53
Last Modified:	14 Jun 2023 10:05
URI:	https://archive.lstmed.ac.uk/id/eprint/20865

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