2la Paracentric Chromosomal Inversion And Overexpressed Metabolic Genes Enhance Thermotolerance And Pyrethroid Resistance In The Major Malaria Vector Anopheles Gambiae

Simple Summary While shifts in temperature may promote the spread of insects, exacerbating the intensity of vector-borne diseases like malaria, very high temperatures exert deleterious effects in insect vectors, forcing them to evolve/adapt genetically. These genetic adaptations may facilitate insecticide resistance through common genes involved in both processes. Here, the impact of thermal tolerance on pyrethroid resistance in the major malaria vector Anopheles gambiae s.l. from four localities spanning the savanna and sub-Sahel of northern Nigeria was investigated. In all four localities, An. coluzzii and An. gambiae s.s. were the only malaria vectors found. The populations were highly thermotolerant, with similar to 50% of mosquitoes in two sites surviving 44 degrees C. Thermotolerant larvae and adult mosquitoes (survivors of 44 degrees C) were significantly more resistant to permethrin, suggesting that prior heat-hardening facilitates insecticide resistance. Thermal tolerance and permethrin resistance were found to be associated with the 2La rearrangement (a form of chromosomal inversion). Transcriptional analysis revealed six major genes commonly overexpressed in the highly thermotolerant mosquitoes and those resistant to permethrin, suggesting common mechanisms involved in thermotolerance and insecticide resistance. These findings highlight challenges associated with insecticide-based malaria vector control, stressing the need to take environmental variables and other pleiotropic mechanisms into account for the choice of control measures.Changes in global temperature are impacting the spread/intensity of vector-borne diseases, including malaria, and accelerating evolutionary/adaptive changes in vector species. These changes, including chromosomal inversions and overexpression and/or changes in allele frequencies of thermotolerance-associated genes, may facilitate insecticide resistance through pleiotropy. This study investigated the impact of thermotolerance on pyrethroid resistance in four populations of the malaria vector An. gambiae s.l., from the savanna/sub-Sahel of northern Nigeria. Anopheles coluzzii and An. gambiae s.s. were the only malaria vectors found, sympatric in all the sites, with the former species predominant. High thermotolerance was observed, with no mortality at 38 degrees C, and LT50 of similar to 44 degrees C. Significantly high permethrin resistance was observed (mortality < 50%) in 44 degrees C heat-hardened (exposure to an intermediately high temperature provides protection to a more severe temperature or insecticide) larvae from two sites, BUK and Pantami, compared with the control, and heat-hardened adult females from Auyo (mortality = 3.00% +/- 1.20, chi(2) = 5.83, p < 0.01) compared with the control (12.00% +/- 4.65). The 2La chromosomal inversion was detected at similar to 50% in subset of larvae and 58% in subset of adult females genotyped. A significant association was observed (OR = 7.2, p < 0.03) between permethrin resistance and the 2La/+(a) rearrangement compared with 2L+(a)/+(a), in BUK larvae. For all sites, permethrin resistance correlated with 2La/a homozygosity in adult females (R = 5.02, p = 0.01). qRT-PCR identified six genes commonly induced/overexpressed, including the heat shock protein 70 (AGAP004581) which was 2468x and 5x overexpressed in heat-hardened and permethrin-resistant females, respectively; trehalose-6-phosphate synthase (AGAP008227); and the ionotropic glutamate receptor genes, IR25a (AGAP010272) and IR21a (AGAP008511). This study highlights challenges associated with insecticide-based malaria vector control, and the epidemiological significance of taking climate variables into account for the design/choice of control measures.