在科特迪瓦各地，四种选定的细胞色素P450（CYPs）在拟除虫菊酯抗性（）和中的参与水平。

Level of involvement of four selected cytochrome P450s (CYPs) in pyrethroid-resistant () and across Côte d'Ivoire.

作者信息

Chabi Joseph, Edi Constant V A, Kouassi Bernard L, Gbalegba Constant N G, Kouassi Armand E, Kouame Jackson K I, Kadio Yves K A, Yokoly Firmain N, Golou Louise B, Gouaméné Janice, Assamoi Jean-Baptiste, Tia Emmanuel, Yapo Roseline M, Konan Lucien Y, N'Tamon Roméo N, Koffi Alphonsine A, Tanoh Antoine M, Ging-Cissé Ndombour, Zinzindohoué Pascal, Kouadio Blaise, Yepassis-Zembrou Patricia L, Irish Seth R, Flatley Cecilia, Kirby Matthew

机构信息

U.S. President's Malaria Initiative, Evolve Project, Washington DC, USA.

Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Cote d'Ivoire.

出版信息

Curr Res Parasitol Vector Borne Dis. 2024 Oct 19;6:100223. doi: 10.1016/j.crpvbd.2024.100223. eCollection 2024.

In Côte d'Ivoire, there is a high intensity of pyrethroid resistance in malaria vectors which may threaten successful vector control. Molecular studies of the target site mutation in the voltage-gated sodium channel (VGSC) show that the gene frequencies of these mutations are high, widely spread across Côte d'Ivoire, and even fixed in some areas. To further characterize insecticide resistance in Côte d'Ivoire beyond target site mutations, the metabolic resistance mechanism was explored. Overexpression of the metabolic enzyme cytochrome , , , and was investigated in () and collected from 30 insecticide resistance monitoring sites across the country in 2021 and 2022. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was carried out using RNA-later preserved 60 surviving mosquitoes from each site after phenotypic susceptibility tests. Additionally, a subsample of about 100 mosquitoes from each site was identified to species by PCR, and the frequency of the VGSC and was determined. All four CYPs were found to be overexpressed in Côte d'Ivoire with at least one CYP statistically significantly overexpressed in 27 of the 30 sites investigated compared to the susceptible () Kisumu ( < 0.005). was overexpressed in 89% of sites and was the sole overexpressed gene in 10 sites, while the overexpression of was found in only 10 sites. and were overexpressed in 16 and 13 sites, respectively. Furthermore, seven sites (Adzopé, Bongouanou, Daloa, Gagnoa, Guiglo Jacqueville, and Sassandra) had overexpression of all four CYPs. Overall, showed higher overexpression of CYPs than (). This study highlights the involvement of selected CYPs in insecticide resistance where target site mutation genes are already present, suggesting that insecticide resistance is complex and multifaceted at a molecular level. Where feasible, it may be helpful to include metabolic resistance surveillance to further characterize insecticide resistance.

在科特迪瓦，疟疾病媒对拟除虫菊酯的抗性强度很高，这可能会威胁到病媒控制的成功。对电压门控钠通道（VGSC）中靶位点突变的分子研究表明，这些突变的基因频率很高，在科特迪瓦广泛分布，甚至在某些地区固定存在。为了进一步表征科特迪瓦除靶位点突变外的杀虫剂抗性，对代谢抗性机制进行了探索。在2021年和2022年从该国30个杀虫剂抗性监测点收集的冈比亚按蚊（Anopheles gambiae）和阿拉伯按蚊（Anopheles arabiensis）中，研究了代谢酶细胞色素P450 1A（CYP1A）、细胞色素P450 2B（CYP2B）、细胞色素P450 2C（CYP2C）和细胞色素P450 6P（CYP6P）的过表达情况。在进行表型易感性试验后，使用RNA Later保存的每个监测点的60只存活蚊子进行定量实时聚合酶链反应（qRT-PCR）分析。此外，通过PCR对每个监测点约100只蚊子的子样本进行物种鉴定，并测定VGSC L1014F和N1575Y的频率。发现所有四种细胞色素P450在科特迪瓦均有过表达，与敏感的肯尼亚基苏木按蚊（Anopheles gambiae Kisumu）相比，在30个调查监测点中的27个监测点中，至少有一种细胞色素P450有统计学意义的过表达（P<0.005）。CYP6P在89%的监测点中过表达，在10个监测点中是唯一过表达的基因，而CYP2C仅在10个监测点中过表达。CYP1A和CYP2B分别在16个和13个监测点中过表达。此外，7个监测点（阿佐佩、邦古阿努、达洛亚、加尼奥阿、吉格洛、雅克维尔和萨桑德拉）所有四种细胞色素P450均有过表达。总体而言，冈比亚按蚊比阿拉伯按蚊表现出更高的细胞色素P450过表达。这项研究突出了所选细胞色素P450在已有靶位点突变基因的情况下参与杀虫剂抗性，表明在分子水平上杀虫剂抗性是复杂且多方面的。在可行的情况下，纳入代谢抗性监测可能有助于进一步表征杀虫剂抗性。