Correction: Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes

Corby‐Harris, Vanessa; Drexler, Anna; Jong, Laurel Watkins de; Antonova, Yevgeniya; Pakpour, Nazzy; Ziegler, Rolf; Ramberg, Frank B.; Lewis, Edwin E.; Brown, John F.; Luckhart, Shirley; Riehle, Michael A.

doi:10.1371/annotation/738ac91f-8c41-4bf5-9a39-bddf0b777a89

Cited by 66 publications

(9 citation statements)

References 40 publications

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“…However, there is a dichotomy in the functional role of insulin signals in activation of the immune response. For example, in the mosquito Anopheles stephensi , increased Akt/PKB signaling in the midgut significantly reduces malaria parasite development compared to control mosquitoes (Corby-Harris et al, 2010). The brain of the mosquito Aedes aegypti releases insulin-like peptides (ILPs) in response to a blood meal.…”

Section: Enhanced Stress Tolerancementioning

confidence: 99%

Insulin signaling and the regulation of insect diapause

Sim¹,

Denlinger²

2013

Front. Physiol.

198

167

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A rich chapter in the history of insect endocrinology has focused on hormonal control of diapause, especially the major roles played by juvenile hormones (JHs), ecdysteroids, and the neuropeptides that govern JH and ecdysteroid synthesis. More recently, experiments with adult diapause in Drosophila melanogaster and the mosquito Culex pipiens, and pupal diapause in the flesh fly Sarcophaga crassipalpis provide strong evidence that insulin signaling is also an important component of the regulatory pathway leading to the diapause phenotype. Insects produce many different insulin-like peptides (ILPs), and not all are involved in the diapause response; ILP-1 appears to be the one most closely linked to diapause in C. pipiens. Many steps in the pathway leading from perception of daylength (the primary environmental cue used to program diapause) to generation of the diapause phenotype remain unknown, but the role for insulin signaling in mosquito diapause appears to be upstream of JH, as evidenced by the fact that application of exogenous JH can rescue the effects of knocking down expression of ILP-1 or the Insulin Receptor. Fat accumulation, enhancement of stress tolerance, and other features of the diapause phenotype are likely linked to the insulin pathway through the action of a key transcription factor, FOXO. This review highlights many parallels for the role of insulin signaling as a regulator in insect diapause and dauer formation in the nematode Caenorhabditis elegans.

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Section: Enhanced Stress Tolerancementioning

confidence: 99%

Insulin signaling and the regulation of insect diapause

Sim¹,

Denlinger²

2013

Front. Physiol.

198

167

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“…The modification of vector genes involved in immunity and vector-parasite interactions or the introduction of exogenous effectors, such as antimicrobial peptides and antibodies specifically targeting the parasite, are the two cardinal approaches to interfere with Plasmodium transmission. A growing set of anti-pathogen effectors now exists (Corby-Harris et al, 2010; Isaacs et al, 2011; Ito et al, 2002; Jasinskiene et al, 2007; Kim et al, 2004), yet these traits have been assessed exclusively against laboratory strains of Plasmodium falciparum or the rodent parasite Plasmodium berghei . Thus, the efficacy of these effectors against genetically diverse polymorphic isolates of the parasite is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Integral gene drives for population replacement

et al. 2018

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A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population, while drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy.

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“…An. stephensi (Liston) mosquitoes were reared as described previously [32]. Briefly, mosquitoes were maintained at 27 • C and 70% humidity on a 16:8 h day:night cycle.…”

Section: Mosquitoesmentioning

confidence: 99%

“…The Anopheles gambiae carboxypeptidase (CP) promoter was modified to remove the signal peptide, start methionine and Kozak consensus sequence and ligated into the phsp-pBac shuttle plasmid containing a SV40 3' UTR as described in Corby-Harris [32]. The kinase-encoding domain of the An.…”

Section: Generation Of Tg An Stephensi Overexpressing Ampkαt176d Under the Control Of The Midgut-and Bloodmeal-specific Carboxypeptidase mentioning

confidence: 99%

Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance

Oringanje¹,

Delacruz

Han

et al. 2021

Genes

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Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly all eukaryotic cells. When activated, AMPK inhibits anabolic pathways that consume ATP and activates catabolic processes that synthesize ATP. In this study, we overexpressed a truncated and constitutively active α-subunit of AMPK under the control of the midgut-specific carboxypeptidase promotor in the midgut of female Anopheles stephensi. As expected, AMPK overexpression in homozygous transgenic mosquitoes was associated with changes in nutrient storage and metabolism, decreasing glycogen levels at 24 h post-blood feeding when transgene expression was maximal, and concurrently increasing circulating trehalose at the same time point. When transgenic lines were challenged with Plasmodium falciparum, we observed a significant decrease in the prevalence and intensity of infection relative to wild type controls. Surprisingly, we did not observe a significant difference in the survival of adult mosquitoes fed either sugar only or both sugar and bloodmeals throughout adult life. This may be due to the limited period that the transgene was activated before homeostasis was restored. However, we did observe a significant decrease in egg production, suggesting that manipulation of AMPK activity in the mosquito midgut resulted in the re-allocation of resources away from egg production. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction, and innate immunity in An. stephensi, a highly invasive and important malaria vector species.

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Correction: Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes

Cited by 66 publications

References 40 publications

Insulin signaling and the regulation of insect diapause

Insulin signaling and the regulation of insect diapause

Integral gene drives for population replacement

Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance

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