Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte Contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
PLoS One. 2013 Apr 23;8(4):e61408. doi: 10.1371/journal.pone.0061408. Print 2013.
In the city of Yaoundé in Cameroon malaria is predominately transmitted by the M and S molecular forms of Anopheles gambiae and both are resistant to the pyrethroid insecticides and DDT. Mutations in the target site of these insecticides, present at a high frequency in malaria vectors in this city, contribute to this resistance profile. To identify additional resistance mechanisms, the expression profile of multiple DDT-resistant field populations of M and S molecular forms was compared to laboratory-susceptible populations.
METHODOLOGY/PRINCIPAL FINDINGS: The prevalence of DDT resistance was highest in the S form population originating from the cultivated site of Nkolondom (mortality after WHO bioassay = 4%). A high prevalence of DDT resistance was also found in two urban M form populations, Messa from a pristine unpolluted environment (DDT mortality = 54%), and Gare, where the breeding sites are heavily polluted with organic matter (DDT mortality = 38%). Microarray analysis showed that several transcripts coding for detoxification enzymes (P450s, GSTs and UDPGTs) and ABC transporters were upregulated in the three populations. Despite the presence of multiple detoxification genes over expressed in the DDT-resistant subset of these field populations, only three were commonly over expressed in resistant populations from all three environments. Two of these genes, CYP6M2 and GSTD1-6, encode enzymes that have been previously shown to metabolize DDT.
CONCLUSION/SIGNIFICANCE: Analogous to target site resistance, genes involved in metabolic resistance to DDT are also shared between the M and S forms of An gambiae. Alternative explanations for this occurrence are explored.
在喀麦隆雅温得市,疟疾主要由 M 和 S 分子形式的冈比亚按蚊传播,两者均对拟除虫菊酯类杀虫剂和滴滴涕具有抗药性。这些杀虫剂的靶标位点突变在该市疟疾媒介中高频存在,导致了这种抗药性特征。为了确定其他的抗药性机制,对多个滴滴涕抗性现场种群的 M 和 S 分子形式的表达谱与实验室敏感种群进行了比较。
方法/主要发现:源自耕作地点 Nkolondom 的 S 种群对滴滴涕的抗性最高(世界卫生组织生物测定后的死亡率为 4%)。两个城市 M 种群也存在很高的滴滴涕抗性,其中 Messa 来自原始未受污染的环境(滴滴涕死亡率为 54%),Gare 的繁殖地受到有机物质的严重污染(滴滴涕死亡率为 38%)。微阵列分析显示,编码解毒酶(P450s、GSTs 和 UDPGTs)和 ABC 转运蛋白的几种转录本在这三个种群中上调。尽管在这些现场种群的滴滴涕抗性亚群中存在多个过度表达的解毒基因,但只有三个在所有三个环境中的抗性种群中共同过度表达。这两个基因,CYP6M2 和 GSTD1-6,编码的酶以前已经被证明可以代谢滴滴涕。
结论/意义:与靶标部位的抗性类似,参与滴滴涕代谢抗性的基因在 M 和 S 型冈比亚按蚊之间也是共有的。对于这种情况发生的其他解释进行了探讨。