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Abstract：
Metabolic resistance to insecticides threatens malaria control. However, little is known about its fitness cost in field populations of malaria vectors, thus limiting the design of suitable resistance management strategies. Here, we assessed the association between the glutathione S-transferase GSTe2-mediated metabolic resistance and life-traits of natural populations of Anopheles funestus. A total of 1200 indoor resting blood-fed female An. funestus (F₀) were collected in Mibellon, Cameroon (2016/2017), and allowed to lay eggs individually. Genotyping of F1 mosquitoes for the L119F-GSTE2 mutation revealed that L/L119-homozygote susceptible (SS) mosquitoes significantly laid more eggs than heterozygotes L119F-RS (odds ratio (OR) = 2.06; p < 0.0001) and homozygote resistant 119F/F-RR (OR = 2.93; p < 0.0001). L/L119-SS susceptible mosquitoes also showed the higher ability for oviposition than 119F/F-RR resistant (OR = 2.68; p = 0.0002) indicating a reduced fecundity in resistant mosquitoes. Furthermore, L119F-RS larvae developed faster (nine days) than L119F-RR and L119F-SS (11 days) (X² = 11.052; degree of freedom (df) = 4; p = 0.02) suggesting a heterozygote advantage effect for larval development. Interestingly, L/L119-SS developed faster than 119F/F-RR (OR = 5.3; p < 0.0001) revealing an increased developmental time in resistant mosquitoes. However, genotyping and sequencing revealed that L119F-RR mosquitoes exhibited a higher adult longevity compared to RS (OR > 2.2; p < 0.05) and SS (OR > 2.1; p < 0.05) with an increased frequency of GSTe2-resistant haplotypes in mosquitoes of D30 after adult emergence. Additionally, comparison of the expression of GSTe2 revealed a significantly increased expression from D1-D30 after emergence of adults (Anova test (F) = 8; df= 3; p = 0.008). The negative association between GSTe2 and some life traits of An. funestus could facilitate new resistance management strategies. However, the increased longevity of GSTe2-resistant mosquitoes suggests that an increase in resistance could exacerbate malaria transmission.
摘要：
对杀虫剂的代谢抗性威胁着疟疾的控制。然而,对它在疟疾病媒野外种群中的适应成本知之甚少，从而限制了合适的阻力管理策略的设计。这里,我们评估了谷胱甘肽S-转移酶GSTe2介导的代谢抗性与按蚊自然种群生活性状之间的关联.共有1200名室内静息用血喂养的女性安。funestus（F0）在Mibellon收集，喀麦隆（2016/2017），并允许单独产卵。F1蚊子对L119F-GSTE2突变的基因分型显示，L/L119纯合子易感（SS）蚊子产卵明显多于杂合子L119F-RS（比值比（OR）=2.06；p<0.0001）和纯合子抗性119F/F-RR（OR=2.93；p<0.0001）。L/L119-SS易感蚊子也显示出比119F/F-RR抗性更高的产卵能力（OR=2.68；p=0.0002），表明抗性蚊子的繁殖力降低。此外，L119F-RS幼虫的发育速度（9天）比L119F-RR和L119F-SS（11天）快（X²=11.052；自由度（df）=4；p=0.02），表明杂合子对幼虫发育的优势作用。有趣的是,L/L119-SS的发育速度快于119F/F-RR（OR=5.3；p<0.0001），表明抗性蚊子的发育时间增加。然而,基因分型和测序显示，与RS（OR>2.2；p<0.05）和SS（OR>2.1；p<0.05）相比，L119F-RR蚊子表现出更高的成年寿命，并且GSTe2抗性单倍型的频率增加成年后出现D30。此外,GSTe2表达的比较显示，成年后D1-D30的表达显着增加（Anova检验（F）=8；df=3；p=0.008）。GSTe2与An的某些生活特征之间的负相关。funestus可以促进新的抗药性管理策略。然而,GSTe2抗性蚊子的寿命延长表明，抗药性的增加可能会加剧疟疾的传播。
