2La Paracentric Chromosomal Inversion and Overexpressed Metabolic Genes Enhance Thermotolerance and Pyrethroid Resistance in the Major Malaria Vector <i>Anopheles gambiae</i>

• Main Authors: Sulaiman S. Ibrahim, Muhammad M. Mukhtar, Abdullahi Muhammad, Charles S. Wondji
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Biology
• Subjects: malaria; <i>Anopheles</i>; coluzzii; <i>gambiae s.s.</i>; 2La; chromosomal
• Online Access: https://www.mdpi.com/2079-7737/10/6/518

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 <i>An. gambiae s.l.,</i> from the savanna/sub-Sahel of northern Nigeria. <i>Anopheles coluzzii</i> and <i>An. gambiae s.s.</i> 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 °C, and LT₅₀ of ~44 °C. Significantly high permethrin resistance was observed (mortality < 50%) in 44 °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, χ² = 5.83, <i>p</i> < 0.01) compared with the control (12.00% ± 4.65). The 2La chromosomal inversion was detected at ~50% in subset of larvae and 58% in subset of adult females genotyped. A significant association was observed (OR = 7.2, <i>p</i> < 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, <i>p</i> = 0.01). qRT-PCR identified six genes commonly induced/overexpressed, including the heat shock protein 70 (AGAP004581) which was 2468× and 5× overexpressed in heat-hardened and permethrin-resistant females, respectively; trehalose-6-phosphate synthase (AGAP008227); and the ionotropic glutamate receptor genes, <i>IR25a</i> (AGAP010272) and <i>IR21a</i> (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.