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ABC transporters are involved in defense against permethrin insecticide in the malaria vector Anopheles stephensi.

ABSTRACT: Proteins from the ABC family (ATP-binding cassette) represent the largest known group of efflux pumps, responsible for transporting specific molecules across lipid membranes in both prokaryotic and eukaryotic organisms. In arthropods they have been shown to play a role in insecticide defense/resistance. The presence of ABC transporters and their possible association with insecticide transport have not yet been investigated in the mosquito Anopheles stephensi, the major vector of human malaria in the Middle East and South Asian regions. Here we investigated the presence and role of ABCs in transport of permethrin insecticide in a susceptible strain of this mosquito species.To identify ABC transporter genes we obtained a transcriptome from untreated larvae of An. stephensi and then compared it with the annotated transcriptome of Anopheles gambiae. To analyse the association between ABC transporters and permethrin we conducted bioassays with permethrin alone and in combination with an ABC inhibitor, and then we investigated expression profiles of the identified genes in larvae exposed to permethrin.Bioassays showed an increased mortality of mosquitoes when permethrin was used in combination with the ABC-transporter inhibitor. Genes for ABC transporters were detected in the transcriptome, and five were selected (AnstABCB2, AnstABCB3, AnstABCB4, AnstABCmember6 and AnstABCG4). An increased expression in one of them (AnstABCG4) was observed in larvae exposed to the LD50 dose of permethrin. Contrary to what was found in other insect species, no up-regulation was observed in the AnstABCB genes.Our results show for the first time the involvement of ABC transporters in larval defense against permethrin in An. stephensi and, more in general, confirm the role of ABC transporters in insecticide defense. The differences observed with previous studies highlight the need of further research as, despite the growing number of studies on ABC transporters in insects, the heterogeneity of the results available at present does not allow us to infer general trends in ABC transporter-insecticide interactions.

SUBMITTER: Epis S

PROVIDER: S-EPMC4124152 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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ABC transporters are involved in defense against permethrin insecticide in the malaria vector Anopheles stephensi.

Epis Sara S Porretta Daniele D Mastrantonio Valentina V Comandatore Francesco F Sassera Davide D Rossi Paolo P Cafarchia Claudia C Otranto Domenico D Favia Guido G Genchi Claudio C Bandi Claudio C Urbanelli Sandra S

Parasites & vectors 20140729

<h4>Background</h4>Proteins from the ABC family (ATP-binding cassette) represent the largest known group of efflux pumps, responsible for transporting specific molecules across lipid membranes in both prokaryotic and eukaryotic organisms. In arthropods they have been shown to play a role in insecticide defense/resistance. The presence of ABC transporters and their possible association with insecticide transport have not yet been investigated in the mosquito Anopheles stephensi, the major vector ...[more]

PMID: 25073980

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Project description:Small laboratory cage trials of non-drive and gene-drive strains of the Asian malaria vector mosquito, Anopheles stephensi, were used to investigate release ratios and other strain properties for their impact on transgene spread during simulated population modification. We evaluated the effects of transgenes on survival, male contributions to next-generation populations, female reproductive success and the impact of accumulation of gene drive-resistant genomic target sites resulting from nonhomologous end-joining (NHEJ) mutagenesis during Cas9, guide RNA-mediated cleavage. Experiments with a non-drive, autosomally-linked malaria-resistance gene cassette showed 'full introduction' (100% of the insects have at least one copy of the transgene) within 8 weeks (? 3 generations) following weekly releases of 10:1 transgenic:wild-type males in an overlapping generation trial design. Male release ratios of 1:1 resulted in cages where mosquitoes with at least one copy of the transgene fluctuated around 50%. In comparison, two of three cages in which the malaria-resistance genes were linked to a gene-drive system in an overlapping generation, single 1:1 release reached full introduction in 6-8 generations with a third cage at ~80% within the same time. Release ratios of 0.1:1 failed to establish the transgenes. A non-overlapping generation, single-release trial of the same gene-drive strain resulted in two of three cages reaching 100% introduction within 6-12 generations following a 1:1 transgenic:wild-type male release. Two of three cages with 0.33:1 transgenic:wild-type male single releases achieved full introduction in 13-16 generations. All populations exhibiting full introduction went extinct within three generations due to a significant load on females having disruptions of both copies of the target gene, kynurenine hydroxylase. While repeated releases of high-ratio (10:1) non-drive constructs could achieve full introduction, results from the 1:1 release ratios across all experimental designs favor the use of gene drive, both for efficiency and anticipated cost of the control programs.

Project description:The malaria vector Anopheles stephensi is found in wide tracts of Asia and the Middle East. The discovery of its presence for the first time in the island of Sri Lanka in 2017, poses a threat of malaria resurgence in a country which had eliminated the disease in 2013. Morphological and genetic characterization showed that the efficient Indian urban vector form An. stephensi sensu stricto or type form, has recently expanded its range to Jaffna and Mannar in northern Sri Lanka that are in proximity to Tamil Nadu state in South India. Comparison of the DNA sequences of the cytochrome oxidase subunit 1 gene in An. stephensi in Jaffna and Mannar in Sri Lanka and Tamil Nadu and Puducherry states in South India showed that a haplotype that is due to a sequence change from valine to methionine in the cytochrome oxidase subunit 1 present in the Jaffna and Mannar populations has not been documented so far in Tamil Nadu/Puducherry populations. The Jaffna An. stephensi were closer to Tamil Nadu/Puducherry populations and differed significantly from the Mannar populations. The genetic findings cannot differentiate between separate arrivals of the Jaffna and Mannar An. stephensi from Tamil Nadu or a single arrival and dispersion to the two locations accompanied by micro-evolutionary changes. Anopheles stephensi was observed to undergo preimaginal development in fresh and brackish water domestic wells and over ground cement water storage tanks in the coastal urban environment of Jaffna and Mannar. Anopheles stephensi in Jaffna was resistant to the common insecticides deltamethrin, dichlorodiphenyltrichloroethane and Malathion. Its preimaginal development in wells and water tanks was susceptible to predation by the larvivorous guppy fish Poecilia reticulata. The arrival, establishment, and spread of An. stephensi in northern Sri Lanka are analyzed in relation to anthropogenic factors that favor its range expansion. The implications of the findings for global public health challenges posed by malaria and other mosquito-borne diseases are discussed.

Dataset Information

ABC transporters are involved in defense against permethrin insecticide in the malaria vector Anopheles stephensi.

Publications

ABC transporters are involved in defense against permethrin insecticide in the malaria vector Anopheles stephensi.

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