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A sensory appendage protein protects malaria vectors from pyrethroids.

ABSTRACT: Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century¹. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control². Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts.

SUBMITTER: Ingham VA

PROVIDER: S-EPMC6974402 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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A sensory appendage protein protects malaria vectors from pyrethroids.

Ingham Victoria A VA Anthousi Amalia A Douris Vassilis V Harding Nicholas J NJ Lycett Gareth G Morris Marion M Vontas John J Ranson Hilary H

Nature 20191225 7790

Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century<sup>1</sup>. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control<sup>2</sup>. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the l ...[more]

PMID: 31875852

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Project description:Agricultural pesticides may play a crucial role in the selection of resistance in field populations of mosquito vectors. This study aimed to determine the susceptibility level of An. gambiae s.l. to pyrethroids and neonicotinoids in vegetable farms in northern Benin, in West Africa, and the underlying insecticide resistance mechanisms. A survey on agricultural practices was carried out on 85 market gardeners chosen randomly in Malanville and Parakou. Anopheles gambiae s.l. larvae were collected, reared to adult stages, and identified to species level. Susceptibility was tested with impregnated papers (WHO bioassays) or CDC bottles according to the insecticides. Synergists (PBO, DEM, and DEF) were used to screen resistance mechanisms. Allelic frequencies of the kdr (L1014F), kdr (L1014S), N1575Y, and ace-1R G119S mutations were determined in mosquitoes using Taqman PCR. Fertilizers and pesticides were the agrochemicals most used with a rate of 97.78% and 100%, respectively, in Malanville and Parakou. Anopheles coluzzii was the predominant species in Malanville, while An. gambiae was the only species found in Parakou. Bioassays revealed a high resistance of An. gambiae s.l. to pyrethroids and DDT, while a susceptibility to bendiocarb, pyrimiphos-methyl, malathion, and clothianidin was recorded. Resistance to acetamiprid was suspected in mosquitoes from both localities. A lower resistance level was observed when mosquitoes were pre-treated with synergists, then exposed to insecticides. The kdr L1014F mutation was observed in both locations at moderate frequencies (0.50 in Malanville and 0.55 in Parakou). The allelic frequencies of N1575Y and G119S were low in both study sites. This study confirmed the resistance of An. gambiae s.l. to insecticides used in agriculture and public health. It reveals a susceptibility of vectors to bendiocarb, pyrimiphos-methyl, malathion, and clothianidin, thus indicating that these insecticides can be used as an alternative in Benin to control malaria vectors.

Project description:BACKGROUND: The dramatic success of insecticide treated nets (ITNs) and long-lasting insecticidal nets (LLINs) in African countries has been countered by the rapid development of pyrethroid resistance in vector mosquitoes over the past decade. One advantage of the use of pyrethroids in ITNs is their excito-repellency. Use of the excito-repellency of pyrethroids might be biorational, since such repellency will not induce or delay the development of any physiological resistance. However, little is known about the relationship between the mode of insecticide resistance and excito-repellency in pyrethroid-resistant mosquitoes. METHODS: Differences in the reactions of 3 major malaria vectors in western Kenya to pyrethroids were compared in laboratory tests. Adult susceptibility tests were performed using World Health Organization (WHO) test tube kits for F1 progenies of field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s., and laboratory colonies of An. gambiae s.s. and An. arabiensis. The contact repellency to pyrethroids or permethrin-impregnated LLINs (Olyset® Nets) was evaluated with a simple choice test modified by WHO test tubes and with the test modified by the WHO cone bioassay test. RESULTS: Field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s. showed high resistance to both permethrin and deltamethrin. The allelic frequency of the point mutation in the voltage-gated sodium channel (L1014S) in An. gambiae s.s. was 99.3-100%, while no point mutations were detected in the other 2 species. The frequency of takeoffs from the pyrethroid-treated surface and the flying times without contacting the surface increased significantly in pyrethroid-susceptible An. gambiae s.s. and An. arabiensis colonies and wild An. arabiensis and An. funestus s.s. colonies, while there was no significant increase in the frequency of takeoffs or flying time in the An. gambiae s.s. wild colony. CONCLUSION: A different repellent reaction was observed in the field-collected An. gambiae s.s. than in An. arabiensis and An. funestus s.s. It might be that resistant mosquitoes governed by knockdown resistance (kdr) loose repellency to pyrethroids, whereas those lacking kdr maintain high repellency irrespective of their possessing metabolic resistance factors to pyrethroids. Further genetic evaluation is required for the demonstration of the above hypothesis.

Project description:BACKGROUND: The island of Timor lies at the south-eastern edge of Indonesia on the boundary of the Oriental and Australian faunal regions. The country of Timor-Leste, which occupies the eastern part of the island, is malarious, but anopheline faunal surveys and malaria vector incrimination date back to the 1960 s. Over the last decade the malaria vectors of south-east Asia and the south-west Pacific have been intensely studied using molecular techniques that can confirm identification within complexes of isomorphic species. The aim of this study is to accurately identify the Anopheles fauna of Timor-Leste using these techniques. METHODS: The survey was carried out over the period February to June 2001. Standard entomological techniques--human landing collections, larval collections and CO2 baited light traps--were used to collect anophelines from the main geographical regions: coastal plains, inland plains, and highlands. Specimens were processed for identification by morphology and genotyped for the ribosomal DNA ITS2 by restriction analysis and/or DNA sequencing. Phylogenetic relationship of Anopheles sundaicus and Anopheles subpictus individuals was also assessed using DNA sequences from the ITS2 and mitochondrial cytochrome-b. All specimens, other than those from larval surveys, were processed to detect the presence of the Plasmodium parasite circumsporozoite protein by ELISA for vector incrimination. RESULTS: Of 2,030 specimens collected, seven species were identified by morphology: Anopheles barbirostris, Anopheles aconitus, Anopheles annularis, Anopheles maculatus, Anopheles peditaeniatus, An. sundaicus and Anopheles vagus. These were confirmed by molecular analysis with the addition of Anopheles flavirostris and an unidentified species designated here as An. vagus genotype B. This latter species was morphologically similar to An. vagus and An. subpictus and is likely to be the An. subpictus described by other workers for Timor. However, genetically this species showed strong affinities to the An. sundaicus complex. Anopheles vagus was the most common species but was rarely collected coming to bite humans; An. barbirostris and An. vagus genotype B were the two most common species collected in human landing catches and both were found positive for CS protein. CONCLUSIONS: The anopheline fauna of Timor-Leste is of Oriental origin with no evidence of elements from the Australian Region. The existence of species complexes will make the use of morphological markers problematic in the country. Using molecular analysis a number of issues regarding the anopheline fauna of Timor-Leste were resolved and nine putative species of Anopheles were identified; two species: An. barbirostris and An. vagus genotype B, were incriminated as malaria vectors.

Project description:BackgroundThe role of vectors in the transmission of avian malaria parasites is currently understudied. Many studies that investigate parasite-vector relationships use limited trapping techniques and/or identify potential competent vectors in the field in such ways that cannot distinguish between an infected or infectious vector. Without the use of multiple trapping techniques that address the specific biology of diverse mosquito species, and without looking at the infection status of individual mosquitoes, it is not possible to make dependable conclusions on the role of mosquitoes in the transmission of avian malaria parasites.MethodsWe conducted two years of mosquito collections at a riparian preserve in California where a wide diversity of species were collected with multiple trap types. We hypothesized that competent mosquito species can influence the distribution and diversity of avian malaria parasites by acting as a compatibility filter for specific Plasmodium species. To determine the infection status of all individual mosquitoes for Plasmodium species/lineages, amplification within the cytochrome b gene was carried out on over 3000 individual mosquito thoraxes, and for those that tested positive we then repeated the same process for abdomens and salivary glands.ResultsOur data show heterogeneity in the transmissibility of Plasmodium among ornithophillic mosquito species. More specifically, Culex stigmatosoma appears to not be a vector of Plasmodium homopolare, a parasite that is prevalent in the avian population, but is a vector of multiple other Plasmodium species/lineages.ConclusionsOur results suggest that conclusions made on the role of vectors from studies that do not use different mosquito trapping methods should be re-evaluated with caution, as we documented the potential for trapping biases, which may cause studies to miss important roles of specific mosquito species in the transmission of avian malaria. Moreover, we document heterogeneity in the transmission of Plasmodium spp. by mosquitoes can influence Plasmodium diversity and prevalence in specific locations to Plasmodium-vector incompatibilities.

Project description:BackgroundAntibody responses against Anopheles salivary proteins can indicate individual exposure to bites of malaria vectors. The extent to which these salivary proteins are species-specific is not entirely resolved. Thus, a better knowledge of the diversity among salivary protein repertoires from various malaria vector species is necessary to select relevant genus-, subgenus- and/or species-specific salivary antigens. Such antigens could be used for quantitative (mosquito density) and qualitative (mosquito species) immunological evaluation of malaria vectors/host contact. In this study, salivary gland protein repertoires (sialomes) from several Anopheles species were compared using in silico analysis and proteomics. The antigenic diversity of salivary gland proteins among different Anopheles species was also examined.ResultsIn silico analysis of secreted salivary gland protein sequences retrieved from an NCBInr database of six Anopheles species belonging to the Cellia subgenus (An. gambiae, An. arabiensis, An. stephensi and An. funestus) and Nyssorhynchus subgenus (An. albimanus and An. darlingi) displayed a higher degree of similarity compared to salivary proteins from closely related Anopheles species. Additionally, computational hierarchical clustering allowed identification of genus-, subgenus- and species-specific salivary proteins. Proteomic and immunoblot analyses performed on salivary gland extracts from four Anopheles species (An. gambiae, An. arabiensis, An. stephensi and An. albimanus) indicated that heterogeneity of the salivary proteome and antigenic proteins was lower among closely related anopheline species and increased with phylogenetic distance.ConclusionThis is the first report on the diversity of the salivary protein repertoire among species from the Anopheles genus at the protein level. This work demonstrates that a molecular diversity is exhibited among salivary proteins from closely related species despite their common pharmacological activities. The involvement of these proteins as antigenic candidates for genus-, subgenus- or species-specific immunological evaluation of individual exposure to Anopheles bites is discussed.

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A sensory appendage protein protects malaria vectors from pyrethroids.

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A sensory appendage protein protects malaria vectors from pyrethroids.

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