Selection for insecticide resistance can promotePlasmodium falciparuminfection inAnopheles

AbstractInsecticide resistance is under strong selective pressure inAnophelesmosquitoes due to widespread usage of insecticides in vector control strategies. Resistance mechanisms likely cause changes that profoundly affect mosquito physiology, yet it remains poorly understood how selective pressures imposed by insecticides may alter the ability of the mosquito to host and transmit aPlasmodiuminfection. From pyrethroid-resistant field-derivedAnopheles gambiae s.l. mosquitoes, we performed selection experiments to establish resistant (RES) and susceptible (SUS) colonies by either selection for, or loss of, insecticide resistance. We show increased prevalence, intensity, and oocyst growth rate ofPlasmodium falciparuminfection in RES females compared to SUS. The increase in infection intensity in RES females was not associated with the presence of thekdrL1014F mutation, and was not impacted by inhibition of Cytochrome P450s. The lipid transporter lipophorin (Lp), which was upregulated in RES compared to SUS, was at least partly implicated in the increased intensity ofP. falciparumbut not directly in the insecticide resistance phenotype. Interestingly, we observed that althoughP. falciparuminfections were not affected when RES females were exposed to permethrin, these females had decreased lipid abundance in the fat body following exposure, pointing to a possible role for lipid mobilization in response to damage caused by insecticide challenge. The finding that selection for insecticide resistance can increaseP. falciparuminfection intensities and growth rate reinforces the need to assess the overall impact on malaria transmission dynamics of selective pressures mosquitoes experience during repeated insecticide challenge.Significance StatementInsecticide resistance poses a severe threat for malaria control. Resistance to pyrethroid insecticides, the active component of most insecticide-treated nets, is now widespread in sub-Saharan Africa, reducing the efficacy of these crucial tools. Despite significant research characterizing insecticide resistance mechanisms, it remains unknown how these traits influencePlasmodium falciparuminfections in malaria-transmittingAnophelesmosquitoes. We established a pyrethroid-resistant and pyrethroid-susceptible population ofAnopheles gambiaederived from the same genetic background and performed experimental infections withP. falciparum. We found that the pyrethroid-resistant population was more supportive of malaria parasites compared to the susceptible population. This was not caused by well-known insecticide resistance mechanisms, but linked with a lipid transporter, lipophorin, which may play an indirect role in resistance.