The molecular basis of insecticide resistance in mosquitoes.

Mosquito-borne diseases, the most well known of which is malaria, are among the leading causes of human deaths worldwide. Vector control is a very important part of the global strategy for management of mosquito-associated diseases, and insecticide application is the most important component in this effort. However, mosquito-borne diseases are now resurgent, largely because of the insecticide resistance that has developed in mosquito vectors and the drug resistance of pathogens. A large number of studies have shown that multiple, complex resistance mechanisms—in particular, increased metabolic detoxification of insecticides and decreased sensitivity of the target proteins—or genes are likely responsible for insecticide resistance. Gene overexpression and amplification, and mutations in protein-coding-gene regions, have frequently been implicated as well. However, no comprehensive understanding of the resistance mechanisms or regulation involved has yet been developed. This article reviews current knowledg...

Insecticide Resistance in Mosquitoes: Impact, Mechanisms, and Research Directions

High insecticide resistance resulting from insensitive acetylcholinesterase (AChE) has emerged in mosquitoes. A single mutation (G119S of the ace-1 gene) explains this high resistance in Culex pipiens and in Anopheles gambiae. In order to provide better documentation of the ace-1 gene and the effect of the G119S mutation, we present a three-dimension structure model of AChE, showing that this unique substitution is localized in the oxyanion hole, explaining the insecticide insensitivity and its interference with the enzyme catalytic functions. As the G119S creates a restriction site, a simple PCR test was devised to detect its presence in both A. gambiae and C. pipiens, two mosquito species belonging to different subfamilies (Culicinae and Anophelinae). It is possibile that this mutation also explains the high resistance found in other mosquitoes, and the present results indicate that the PCR test detects the G119S mutation in the malaria vector A. albimanus. The G119S has thus occurred independently at least four times in mosquitoes and this PCR test is probably of broad applicability within the Culicidae family.

/pdf/the-unique-mutation-in-ace-1-giving-high-insecticide-1v980io5s6.pdf

The unique mutation in ace-1 giving high insecticide resistance is easily detectable in mosquito vectors.

Adaptation in eukaryotes is generally assumed to be mutation-limited because of small effective population sizes. This view is difficult to reconcile, however, with the observation that adaptation to anthropogenic changes, such as the introduction of pesticides, can occur very rapidly. Here we investigate adaptation at a key insecticide resistance locus (Ace) in Drosophila melanogaster and show that multiple simple and complex resistance alleles evolved quickly and repeatedly within individual populations. Our results imply that the current effective population size of modern D. melanogaster populations is likely to be substantially larger (≥100-fold) than commonly believed. This discrepancy arises because estimates of the effective population size are generally derived from levels of standing variation and thus reveal long-term population dynamics dominated by sharp—even if infrequent—bottlenecks. The short-term effective population sizes relevant for strong adaptation, on the other hand, might be much closer to census population sizes. Adaptation in Drosophila may therefore not be limited by waiting for mutations at single sites, and complex adaptive alleles can be generated quickly without fixation of intermediate states. Adaptive events should also commonly involve the simultaneous rise in frequency of independently generated adaptive mutations. These so-called soft sweeps have very distinct effects on the linked neutral polymorphisms compared to the standard hard sweeps in mutation-limited scenarios. Methods for the mapping of adaptive mutations or association mapping of evolutionarily relevant mutations may thus need to be reconsidered.

/pdf/evidence-that-adaptation-in-drosophila-is-not-limited-by-5atlci3rpw.pdf

Evidence that adaptation in Drosophila is not limited by mutation at single sites.

"The publication of the extensive seven-volume work Comprehensive Molecular Insect Science provided a complete reference encompassing important developments and achievements in modern insect science, including reviews on the ecdysone receptor, lipocalins, and bacterial toxins. Now two editors of the original series, Drs. Lawrence I. Gilbert and Sarjeet S. Gill, have selected contributions for a special volume of compelling and timeless articles on key aspects of insect pharmacology. Insect Pharmacology includes articles and new addenda covering sodium channels, spider toxins and their potential for insect control, insect transformation for use in control, amino acid and neurotransmitter transporters, and more." "This single-volume was created for the researcher, entomologist, or student with a specialized interest in insect pharmacology."  [Book Jacket]

Biochemical genetics and genomics of insect esterases

https://www3.nd.edu/~dseverso/Pubs/Nabeshima_BBRC_2004.pdf

An amino acid substitution attributable to insecticide-insensitivity of acetylcholinesterase in a Japanese encephalitis vector mosquito, Culex tritaeniorhynchus.

Absence of protein polymorphism attributable to insecticide-insensitivity of acetylcholinesterase in the green rice leafhopper, Nephotettix cincticeps.

Osamu Hidoh

Papers

An amino acid substitution attributable to insecticide-insensitivity of acetylcholinesterase in a Japanese encephalitis vector mosquito, Culex tritaeniorhynchus.

Absence of protein polymorphism attributable to insecticide-insensitivity of acetylcholinesterase in the green rice leafhopper, Nephotettix cincticeps.