Widespread occurrence of copy number variants and fixation of pyrethroid target site resistance in Anopheles gambiae (s.l.) from southern Côte d'Ivoire.
Widespread occurrence of copy number variants and fixation of pyrethroid target site resistance in Anopheles gambiae (s.l.) from southern Côte d'Ivoire.
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DOI：
10.1016/j.crpvbd.2023.100117
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Lucas, Eric
中科院分区：
文献类型：
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作者：
Kouame, Ruth M A;Lynd, Amy;Kouame, Jackson K I;Vavassori, Laura;Abo, Kouabenan;Donnelly, Martin J;Edi, Constant;Lucas, Eric
冈比亚按蚊对拟除虫菊酯和有机磷杀虫剂的抗药性由多种基因突变赋予，包括单核苷酸多态性（SNP）和拷贝数变异（CNV）。了解这些突变在蚊子种群中的分布是制定更好的管理策略的先决条件。本研究共采集冈比亚按蚊（Anopheles gambiae（s.l.）来自科特迪瓦南部的2000名受试者暴露于溴氰菊酯或甲基嘧啶杀虫剂，并进行筛选以评估已知或认为赋予对一种或另一种杀虫剂类别抗性的SNP和CNV的分布。大多数人从一个。冈比亚（s.l.）经分子生物学鉴定为科氏按蚊（Anopheles coluzzii）。溴氰菊酯的存活率（94%至97%）高于甲基吡嘧磺隆（10%至49%）。在安。冈比亚（s.s.），电压门控钠通道（Vgsc）中995 F位点的SNP（Vgsc-995 F）是固定的，而其它靶位点突变是罕见的或不存在的（Vgsc-402 L：0%; Vgsc-1570 Y：0%，乙酰胆碱酯酶Acel-280 S：14%）。在安。在coluzzii中，Vgsc-995 F是以最高频率（65%）发现的靶位点SNP，其次是其他靶位点突变（Vgsc-402 L：36%; Vgsc-1570 Y：0.33%; Acel-280 S：45%）。Vgsc-995 S SNP不存在。发现Ace 1 - 280 S SNP的存在与Ace 1-CNV，Ace1_AgDup的存在显著相关。Ace1_AgDup的存在与抗嘧啶核苷耐药性之间存在显著关联。冈比亚（s.s.）但不是在安。猫猴。Ace1_Del97缺失在1例安氏按蚊中发现。冈比亚（s.s.）在Cyp 6aa/Cyp 6p基因簇中检测到4个CNV，该基因簇包含已知的重要抗性基因。coluzzii，最常见的是Dup 7（42%）和Dup 14（26%）。虽然这些个体CNV等位基因均与抗性无显著相关性，但Cyp 6aa基因区域的拷贝数通常与溴氰菊酯抗性增加相关。Cyp 6p 3的高表达几乎与溴氰菊酯抗性相关，尽管抗性与拷贝数无关。使用替代杀虫剂和控制方法，以阻止抗药性在安。coluzzii种群是值得的。Vgsc-995 F突变在An.冈比亚（s.s.）Vgsc-402 L等位基因在安徽省汉族人群中的频率为36%。猫猴。Ace 1 - 280 S基因型的分布与抗吡嘧磺隆显著相关。代谢基因中的CNV等位基因在存在/不存在水平上与耐药性没有显著相关。Cyp 6aa 2的拷贝数是定量的，与溴氰菊酯抗性呈正相关。
Resistance to pyrethroid and organophosphate insecticides in the malaria vector Anopheles gambiae (s.l.) is conferred by a variety of genetic mutations, including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Knowledge of the distribution of these mutations in mosquito populations is a prerequisite for establishing better strategies for their management. In this study, a total of 755 Anopheles gambiae (s.l.) from southern Côte d’Ivoire were exposed to deltamethrin or pirimiphos-methyl insecticides and were screened to assess the distribution of SNPs and CNVs known or believed to confer resistance to one or other of the insecticide classes. Most individuals from the An. gambiae (s.l.) complex were identified by molecular tests as Anopheles coluzzii. Survival to deltamethrin (from 94% to 97%) was higher than to pirimiphos-methyl (from 10% to 49%). In An. gambiae (s.s.), the SNP in the Voltage Gated Sodium Channel (Vgsc) at the 995F locus (Vgsc-995F) was fixed, while other target site mutations were rare or absent (Vgsc-402L: 0%; Vgsc-1570Y: 0%, Acetylcholinesterase Acel-280S: 14%). In An. coluzzii, Vgsc-995F was the target site SNP found at highest frequency (65%) followed by other target site mutations (Vgsc-402L: 36%; Vgsc-1570Y: 0.33%; Acel-280S: 45%). The Vgsc-995S SNP was not present. The presence of the Ace1-280S SNP was found to be significantly linked to the presence of the Ace1-CNV, Ace1_AgDup. Significant association was found between the presence of the Ace1_AgDup and pirimiphos-methyl resistance in An. gambiae (s.s.) but not in An. coluzzii. The deletion Ace1_Del97 was found in one specimen of An. gambiae (s.s.). Four CNVs in the Cyp6aa/Cyp6p gene cluster, which contains genes of known importance for resistance, were detected in An. coluzzii, the most frequent being Dup 7 (42%) and Dup 14 (26%). While none of these individual CNV alleles were significantly associated with resistance, copy number in the Cyp6aa gene region in general was associated with increased resistance to deltamethrin. Elevated expression of Cyp6p3 was nearly associated with deltamethrin resistance, although there was no association of resistance with copy number. Use of alternative insecticides and control methods to arrest resistance spread in An. coluzzii populations is merited. The Vgsc-995F mutation was fixed in An. gambiae (s.s.). The Vgsc-402L allele was found at a frequency of 36% in An. coluzzii. The distribution of the Ace1-280S genotypes was significantly associated with resistance to pirimiphos-methyl. CNV alleles in metabolic genes were individually not significantly associated with resistance at the presence/absence level. Copy number in Cyp6aa2, which is quantitative, was found to be positively associated with resistance to deltamethrin.