Djouaka Rousseau F, Bakare Adekunle A, Coulibaly Ousmane N, Akogbeto Martin C, Ranson Hilary, Hemingway Janet, Strode Clare
International Institute of Tropical Agriculture, Cotonou, 08BP0932, Benin.
BMC Genomics. 2008 Nov 13;9:538. doi: 10.1186/1471-2164-9-538.
Insecticide resistance in Anopheles mosquitoes is threatening the success of malaria control programmes. This is particularly true in Benin where pyrethroid resistance has been linked to the failure of insecticide treated bed nets. The role of mutations in the insecticide target sites in conferring resistance has been clearly established. In this study, the contribution of other potential resistance mechanisms was investigated in Anopheles gambiae s.s. from a number of localities in Southern Benin and Nigeria. The mosquitoes were sampled from a variety of breeding sites in a preliminary attempt to investigate the role of contamination of mosquito breeding sites in selecting for resistance in adult mosquitoes.
All mosquitoes sampled belonged to the M form of An. gambiae s.s. There were high levels of permethrin resistance in an agricultural area (Akron) and an urban area (Gbedjromede), low levels of resistance in mosquito samples from an oil contaminated site (Ojoo) and complete susceptibility in the rural Orogun location. The target site mutation kdrW was detected at high levels in two of the populations (Akron f = 0.86 and Gbedjromede f = 0.84) but was not detected in Ojoo or Orogun. Microarray analysis using the Anopheles gambiae detox chip identified two P450s, CYP6P3 and CYP6M2 up regulated in all three populations, the former was expressed at particularly high levels in the Akron (12.4-fold) and Ojoo (7.4-fold) populations compared to the susceptible population. Additional detoxification and redox genes were also over expressed in one or more populations including two cuticular pre-cursor genes which were elevated in two of the three resistant populations.
Multiple resistance mechanisms incurred in the different breeding sites contribute to resistance to permethrin in Benin. The cytochrome P450 genes, CYP6P3 and CYP6M2 are upregulated in all three resistant populations analysed. Several additional potential resistance mechanisms were also identified that warrant further investigation. Metabolic genes were over expressed irrespective of the presence of kdr, the latter resistance mechanism being absent in one resistant population. The discovery that mosquitoes collected from different types of breeding sites display differing profiles of metabolic genes at the adult stage may reflect the influence of a range of xenobiotics on selecting for resistance in mosquitoes.
按蚊的杀虫剂抗性正威胁着疟疾控制项目的成效。在贝宁尤其如此，拟除虫菊酯抗性与经杀虫剂处理的蚊帐失效有关。杀虫剂靶位点突变在赋予抗性方面的作用已得到明确证实。在本研究中，对来自贝宁南部和尼日利亚多个地区的冈比亚按蚊中其他潜在抗性机制的作用进行了调查。从各种繁殖地采集蚊子样本，初步尝试调查蚊子繁殖地污染在选择成年蚊子抗性方面的作用。
所有采集的蚊子均属于冈比亚按蚊的M型。在一个农业地区（阿克隆）和一个城市地区（格贝德罗梅德），氯菊酯抗性水平较高；在一个受石油污染的地点（奥乔）采集的蚊子样本中，抗性水平较低；而在农村的奥罗贡地区，蚊子对氯菊酯完全敏感。在其中两个种群（阿克隆f = 0.86，格贝德罗梅德f = 0.84）中检测到高水平的靶位点突变kdrW，但在奥乔或奥罗贡未检测到。使用冈比亚按蚊解毒芯片进行的微阵列分析确定，在所有三个种群中，两种细胞色素P450，即CYP6P3和CYP6M2上调，与敏感种群相比，前者在阿克隆种群（12.4倍）和奥乔种群（7.4倍）中表达水平特别高。其他解毒和氧化还原基因在一个或多个种群中也过度表达，包括两个表皮前体基因，在三个抗性种群中的两个中升高。
不同繁殖地产生的多种抗性机制导致了贝宁的氯菊酯抗性。细胞色素P450基因CYP6P3和CYP6M2在所有三个分析的抗性种群中均上调。还确定了其他几种潜在的抗性机制，值得进一步研究。无论是否存在kdr，代谢基因都过度表达，后一种抗性机制在一个抗性种群中不存在。从不同类型繁殖地采集的蚊子在成年阶段显示出不同的代谢基因谱，这一发现可能反映了一系列外源化合物对选择蚊子抗性的影响。
