Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids.
Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids.
复制标题
现场捕获的耐氯菊酯抗蚊子冈比亚过表达CYP6P3，一种代谢拟除虫菊酯的P450。
DOI：
10.1371/journal.pgen.1000286
复制
发表时间：
2008-11
期刊：
影响因子：
4.5
通讯作者：
Donnelly, Martin J.
中科院分区：
文献类型：
--
作者：
Mueller, Pie;Warr, Emma;Stevenson, Bradley J.;Pignatelli, Patricia M.;Morgan, John C.;Steven, Andrew;Yawson, Alexander E.;Mitchell, Sara N.;Ranson, Hilary;Hemingway, Janet;Paine, Mark J. I.;Donnelly, Martin J.
接触农药的昆虫会经历强烈的自然选择，并发展出各种适应机制来生存。疟疾媒介冈比亚按蚊对拟除虫菊酯杀虫剂的抗药性正受到越来越多的关注，因为它威胁到撒哈拉以南非洲疟疾媒介控制计划的可持续性。了解拟除虫菊酯抗性的分子机制可以深入了解适应性特征的进化过程，并有助于开发简单的监测工具和恢复杀虫剂功效的新策略。为此，有必要了解野生蚊子中哪些机制很重要。在这里，我们的目的是通过测量来自加纳高抗性野生冈比亚种群的表型个体中 250 多个可能与代谢抗性相关的基因的基因表达，来鉴定可能在拟除虫菊酯代谢抗性中起重要作用的酶。细胞色素 P450 CYP6P3 在幸存者中显着过度表达，我们表明翻译的酶可代谢 α-氰基和非 α-氰基拟除虫菊酯。这是第一项证明野生冈比亚冈比亚 P450 代谢杀虫剂能力的研究。这些发现增加了对野生蚊子种群杀虫剂抗药性遗传基础的理解。疟疾是一种由按蚊传播的疾病，是一个全球性健康问题，具有巨大的经济和社会影响。拟除虫菊酯杀虫剂对于减少疟疾传播至关重要，对这些杀虫剂的耐药性威胁着当前的控制工作。由于在可预见的未来，可用的公共卫生杀虫剂数量有限，因此监测耐药性水平至关重要，以便在控制失败之前决定何时实施新策略。对于监测而言，非常需要简单的分子测定，因为它们可以以非常低的频率检测耐药性，并且应该在生物测定之前识别单个隐性等位基因的存在。了解产生抗性的机制有助于开发此类工具，也可能导致恢复杀虫剂功效的新策略或开发新化合物。我们着手通过比较杀虫剂选择的蚊子与未选择的蚊子之间的信使 RNA 水平来鉴定可能赋予代谢拟除虫菊酯抗性的酶。我们捕获了主要疟疾媒介 A. gambiae s.s. 的成员。来自高度拟除虫菊酯抗药性的野外种群。我们发现细胞色素 P450（CYP6P3）的转录水平增加，并证明它编码代谢拟除虫菊酯的酶。
Insects exposed to pesticides undergo strong natural selection and have developed various adaptive mechanisms to survive. Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is receiving increasing attention because it threatens the sustainability of malaria vector control programs in sub-Saharan Africa. An understanding of the molecular mechanisms conferring pyrethroid resistance gives insight into the processes of evolution of adaptive traits and facilitates the development of simple monitoring tools and novel strategies to restore the efficacy of insecticides. For this purpose, it is essential to understand which mechanisms are important in wild mosquitoes. Here, our aim was to identify enzymes that may be important in metabolic resistance to pyrethroids by measuring gene expression for over 250 genes potentially involved in metabolic resistance in phenotyped individuals from a highly resistant, wild A. gambiae population from Ghana. A cytochrome P450, CYP6P3, was significantly overexpressed in the survivors, and we show that the translated enzyme metabolises both alpha-cyano and non–alpha-cyano pyrethroids. This is the first study to demonstrate the capacity of a P450 identified in wild A. gambiae to metabolise insecticides. The findings add to the understanding of the genetic basis of insecticide resistance in wild mosquito populations. Malaria, a disease spread by anopheline mosquitoes, is a global health problem with an enormous economic and social impact. Pyrethroid insecticides are critical in reducing malaria transmission, and resistance to these insecticides threatens current control efforts. With a limited number of public health insecticides available for the foreseeable future, it is vital to monitor levels of resistance to facilitate decisions on when new strategies should be implemented before control fails. For monitoring, simple molecular assays are highly desirable, because they can detect resistance at very low frequencies and should identify the presence of single recessive alleles well before bioassays. An understanding of the mechanisms conferring resistance facilitates the development of such tools and may also lead to novel strategies to restore the efficacy of the insecticide, or the development of new compounds. We set out to identify enzymes that may confer metabolic pyrethroid resistance by comparing levels of messenger RNA between insecticide-selected versus unselected mosquitoes. We caught members of the major malaria vector, A. gambiae s.s. from a highly pyrethroid resistant field population. We found increased transcript levels for a cytochrome P450, CYP6P3, and demonstrate that it encodes for an enzyme that metabolises pyrethroids.
登录
查看更多内容
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
2.6
作者：
Mclaughlin, L. A.;Niazi, U.;Paine, M. J. I.
通讯作者：
Paine, M. J. I.
影响因子：
4.9
作者：
Mueller, Pie;Chouaibou, Mouhamadou;Ranson, Hilary
通讯作者：
Ranson, Hilary
DOI：
10.1073/pnas.0709249105
发表时间：
2008-07-01
影响因子：
11.1
作者：
Chiu, Ting-Lan;Wen, Zhimou;Schuler, Mary A.
通讯作者：
Schuler, Mary A.
影响因子：
2.6
作者：
Ranson, H;Jensen, B;Collins, FH
通讯作者：
Collins, FH