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Cytochrome P450 metabolic resistance (CYP6P9a) to pyrethroids imposes a fitness cost in the major African malaria vector Anopheles funestus
Heredity ( IF 3.1 ) Pub Date : 2020-03-10 , DOI: 10.1038/s41437-020-0304-1 Magellan Tchouakui 1, 2 , Jacob Riveron Miranda 1, 3 , Leon M J Mugenzi 1, 4 , Doumani Djonabaye 1, 5 , Murielle J Wondji 1, 3 , Micareme Tchoupo 1 , Williams Tchapga 1 , Flobert Njiokou 2 , Charles S Wondji 1, 3
Heredity ( IF 3.1 ) Pub Date : 2020-03-10 , DOI: 10.1038/s41437-020-0304-1 Magellan Tchouakui 1, 2 , Jacob Riveron Miranda 1, 3 , Leon M J Mugenzi 1, 4 , Doumani Djonabaye 1, 5 , Murielle J Wondji 1, 3 , Micareme Tchoupo 1 , Williams Tchapga 1 , Flobert Njiokou 2 , Charles S Wondji 1, 3
Affiliation
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Metabolic resistance threatens the sustainability of pyrethroid-based malaria control interventions. Elucidating the fitness cost and potential reversal of metabolic resistance is crucial to design suitable resistance management strategies. Here, we deciphered the fitness cost associated with the CYP6P9a (P450-mediated metabolic resistance) in the major African malaria vector Anopheles funestus. Reciprocal crosses were performed between a pyrethroid susceptible (FANG) and resistant (FUMOZ-R) laboratory strains and the hybrid strains showed intermediate resistance. Genotyping the CYP6P9a-R resistance allele in oviposited females revealed that CYP6P9a negatively impacts the fecundity as homozygote susceptible mosquitoes (CYP6P9a-SS) lay more eggs than heterozygote (OR = 2.04: P = 0.01) and homozygote resistant mosquitoes. CYP6P9a also imposes a significant fitness cost on the larval development as homozygote resistant larvae (CYP6P9a-RR) developed significantly slower than heterozygote and homozygote susceptible mosquitoes (χ2 = 11.2; P = 0.0008). This fitness cost was further supported by the late pupation of homozygote resistant than susceptible mosquitoes (OR = 2.50; P < 0.01). However, CYP6P9a does not impact the longevity as no difference was observed in the life span of mosquitoes with different genotypes (χ2 = 1.6; P = 0.9). In this hybrid strain, a significant decrease of the resistant CYP6P9a-RR genotype was observed after ten generations (χ2 = 6.6; P = 0.01) suggesting a reversal of P450-based resistance in the absence of selection. This study shows that the P450-mediated metabolic resistance imposes a high fitness cost in malaria vectors supporting that a resistance management strategy based on rotation could help mitigate the impact of such resistance.
中文翻译：
对拟除虫菊酯的细胞色素 P450 代谢抗性 (CYP6P9a) 对非洲主要疟疾病媒 Anopheles funestus 施加了健康成本
代谢耐药性威胁到基于拟除虫菊酯的疟疾控制干预措施的可持续性。阐明代谢阻力的健康成本和潜在逆转对于设计合适的阻力管理策略至关重要。在这里，我们破译了与非洲主要疟疾载体 Anopheles funestus 中 CYP6P9a（P450 介导的代谢抗性）相关的健康成本。在拟除虫菊酯敏感 (FANG) 和抗性 (FUMOZ-R) 实验室菌株之间进行互惠杂交，杂交菌株显示中等抗性。对排卵雌性的 CYP6P9a-R 抗性等位基因进行基因分型显示，CYP6P9a 对繁殖力有负面影响，因为纯合子易感蚊子 (CYP6P9a-SS) 比杂合子 (OR = 2.04: P = 0.01) 和纯合子抗性蚊子产卵更多。CYP6P9a 也对幼虫的发育造成显着的适应成本，因为纯合子抗性幼虫 (CYP6P9a-RR) 的发育明显慢于杂合子和纯合子易感蚊子 (χ2 = 11.2; P = 0.0008)。与易感蚊子相比，纯合子的化蛹晚进一步支持了这种适应性成本（OR = 2.50；P < 0.01）。然而，CYP6P9a 不影响寿命，因为不同基因型蚊子的寿命没有差异（χ2 = 1.6; P = 0.9）。在该杂种菌株中，在十代后观察到抗性 CYP6P9a-RR 基因型显着降低（χ2 = 6.6；P = 0.01），表明在没有选择的情况下，基于 P450 的抗性逆转。
更新日期：2020-03-10
中文翻译：
对拟除虫菊酯的细胞色素 P450 代谢抗性 (CYP6P9a) 对非洲主要疟疾病媒 Anopheles funestus 施加了健康成本
代谢耐药性威胁到基于拟除虫菊酯的疟疾控制干预措施的可持续性。阐明代谢阻力的健康成本和潜在逆转对于设计合适的阻力管理策略至关重要。在这里，我们破译了与非洲主要疟疾载体 Anopheles funestus 中 CYP6P9a（P450 介导的代谢抗性）相关的健康成本。在拟除虫菊酯敏感 (FANG) 和抗性 (FUMOZ-R) 实验室菌株之间进行互惠杂交，杂交菌株显示中等抗性。对排卵雌性的 CYP6P9a-R 抗性等位基因进行基因分型显示，CYP6P9a 对繁殖力有负面影响，因为纯合子易感蚊子 (CYP6P9a-SS) 比杂合子 (OR = 2.04: P = 0.01) 和纯合子抗性蚊子产卵更多。CYP6P9a 也对幼虫的发育造成显着的适应成本，因为纯合子抗性幼虫 (CYP6P9a-RR) 的发育明显慢于杂合子和纯合子易感蚊子 (χ2 = 11.2; P = 0.0008)。与易感蚊子相比，纯合子的化蛹晚进一步支持了这种适应性成本（OR = 2.50；P < 0.01）。然而，CYP6P9a 不影响寿命，因为不同基因型蚊子的寿命没有差异（χ2 = 1.6; P = 0.9）。在该杂种菌株中，在十代后观察到抗性 CYP6P9a-RR 基因型显着降低（χ2 = 6.6；P = 0.01），表明在没有选择的情况下，基于 P450 的抗性逆转。
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