Insecticide resistant Anopheles from Ethiopia but not Burkina Faso show a microbiota composition shift upon insecticide exposure.

Background: Malaria remains a key contributor to mortality and morbidity across Africa, with the highest burden in children under 5. Insecticide-based vector control tools, which target the adult Anopheles mosquitoes, are the most efficacious tool in disease prevention. Due to the widespread use of these interventions, insecticide resistance to the most used classes of insecticides is now pervasive across Africa.

Pervasive sublethal effects of agrochemicals on insects at environmentally relevant concentrations.

Insect biomass is declining globally, likely driven by climate change and pesticide use, yet systematic studies on the effects of various chemicals remain limited. In this work, we used a chemical library of 1024 molecules-covering insecticides, herbicides, fungicides, and plant growth inhibitors-to assess the impact of sublethal pesticide doses on insects. In , 57% of chemicals affected larval behavior, and a higher proportion compromised long-term survivability.

Uridine diphosphate (UDP)-glycosyltransferases (UGTs) are associated with insecticide resistance in the major malaria vectors Anopheles gambiae s.l. and Anopheles funestus.

Malaria remains one of the highest causes of morbidity and mortality, with 249 million cases and over 608,000 deaths in 2022. Insecticides, which target the Anopheles mosquito vector, are the primary method to control malaria. The widespread nature of resistance to the most important insecticide class, the pyrethroids, threatens the control of this disease.

Genomic Profiling of Insecticide Resistance in Malaria Vectors: Insights into Molecular Mechanisms.

Malaria control faces challenges from widespread insecticide resistance in major species. This study, employing a cross-species approach, integrates RNA-Sequencing, whole-genome sequencing, and microarray data to elucidate drivers of insecticide resistance in complex and Findings show an inverse relationship between genetic diversity and gene expression, with highly expressed genes experiencing stronger purifying selection. These genes cluster physically in the genome, revealing potential coordinated regulation.

Vector control: agents of selection on malaria parasites?

Insect vectors are responsible for spreading many infectious diseases, yet interactions between pathogens/parasites and insect vectors remain poorly understood. Filling this knowledge gap matters because vectors are evolving in response to the deployment of vector control tools (VCTs). Yet, whilst the evolutionary responses of vectors to VCTs are being carefully monitored, the knock-on consequences for parasite evolution have been overlooked.

Sympatric Populations of the Complex in Southwest Burkina Faso Evolve Multiple Diverse Resistance Mechanisms in Response to Intense Selection Pressure with Pyrethroids.

Pyrethroid resistance in the Anopheles vectors of malaria is driving an urgent search for new insecticides that can be used in proven vector control tools such as insecticide treated nets (ITNs). Screening for potential new insecticides requires access to stable colonies of the predominant vector species that contain the major pyrethroid resistance mechanisms circulating in wild populations. Southwest Burkina Faso is an apparent hotspot for the emergence of pyrethroid resistance in species of the Anopheles gambiae complex.

Capturing the transcription factor interactome in response to sub-lethal insecticide exposure.

The increasing levels of pesticide resistance in agricultural pests and disease vectors represents a threat to both food security and global health. As insecticide resistance intensity strengthens and spreads, the likelihood of a pest encountering a sub-lethal dose of pesticide dramatically increases. Here, we apply dynamic Bayesian networks to a transcriptome time-course generated using sub-lethal pyrethroid exposure on a highly resistant population.

Integration of whole genome sequencing and transcriptomics reveals a complex picture of the reestablishment of insecticide resistance in the major malaria vector Anopheles coluzzii.

Insecticide resistance is a major threat to gains in malaria control, which have been stalling and potentially reversing since 2015. Studies into the causal mechanisms of insecticide resistance are painting an increasingly complicated picture, underlining the need to design and implement targeted studies on this phenotype. In this study, we compare three populations of the major malaria vector An.

Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health.

Background: There is an urgent need for insecticides with novel modes of action against mosquito vectors. Broflanilide is a meta-diamide, discovered and named Tenebenal™ by Mitsui Chemicals Agro, Inc., which has been identified as a candidate insecticide for use in public health products.

A steroid hormone agonist reduces female fitness in insecticide-resistant Anopheles populations.

Insecticide based vector control tools such as insecticide treated bednets and indoor residual spraying represent the cornerstones of malaria control programs. Resistance to chemistries used in these programs is now widespread and represents a significant threat to the gains seen in reducing malaria-related morbidity and mortality. Recently, disruption of the 20-hydroxyecdysone steroid hormone pathway was shown to reduce Plasmodium development and significantly reduce both longevity and egg production in a laboratory susceptible Anopheles gambiae population.

Effects of insecticide resistance and exposure on Plasmodium development in Anopheles mosquitoes.

The spread of insecticide resistance in anopheline mosquitoes is a serious threat to the success of malaria control and prospects of elimination, but the potential impact(s) of insecticide resistance or sublethal insecticide exposure on Plasmodium-Anopheles interactions are poorly understood. Only a few studies have attempted to investigate such interactions, despite their clear epidemiological significance for malaria transmission. This short review provides an update on our understanding of the interactions between insecticide resistance and exposure and Plasmodium development, focusing on the mechanisms which might underpin any interactions, and identifying some key knowledge gaps.

IR-TEx: An Open Source Data Integration Tool for Big Data Transcriptomics Designed for the Malaria Vector Anopheles gambiae.

IR-TEx is an application written in Shiny (an R package) that allows exploration of the expression of (as well as assigning functions to) transcripts whose expression is associated with insecticide resistance phenotypes in Anopheles gambiae mosquitoes. The application can be used online or downloaded and used locally by anyone. The local application can be modified to add new insecticide resistance datasets generated from multiple -omics platforms.

A sensory appendage protein protects malaria vectors from pyrethroids.

Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century. 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. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers pyrethroid resistance to Anopheles gambiae.

Characterisation of Anopheles strains used for laboratory screening of new vector control products.

Background: Insecticides formulated into products that target Anopheles mosquitos have had an immense impact on reducing malaria cases in Africa. However, resistance to currently used insecticides is spreading rapidly and there is an urgent need for alternative public health insecticides. Potential new insecticides must be screened against a range of characterized mosquito strains to identify potential resistance liabilities.

The transcription factor Maf-S regulates metabolic resistance to insecticides in the malaria vector Anopheles gambiae.

Background: Malaria control in Africa is dependent upon the use insecticides but intensive use of a limited number of chemicals has led to resistance in mosquito populations. Increased production of enzymes that detoxify insecticides is one of the most potent resistance mechanisms. Several metabolic enzymes have been implicated in insecticide resistance but the processes controlling their expression have remained largely elusive.

Dissecting the organ specificity of insecticide resistance candidate genes in Anopheles gambiae: known and novel candidate genes.

Background: The elevated expression of enzymes with insecticide metabolism activity can lead to high levels of insecticide resistance in the malaria vector, Anopheles gambiae. In this study, adult female mosquitoes from an insecticide susceptible and resistant strain were dissected into four different body parts. RNA from each of these samples was used in microarray analysis to determine the enrichment patterns of the key detoxification gene families within the mosquito and to identify additional candidate insecticide resistance genes that may have been overlooked in previous experiments on whole organisms.

Glimepiride reduces CD14 expression and cytokine secretion from macrophages.

Background: Activated microglia are associated with deposits of aggregated proteins within the brains of patients with Alzheimer's disease (AD), Parkinson's disease (PD) and prion diseases. Since the cytokines secreted from activated microglia are thought to contribute to the pathogenesis of these neurodegenerative diseases, compounds that suppress cytokine production have been identified as potential therapeutic targets. CD14 is a glycosylphosphatidylinositol (GPI)- anchored protein that is part of a receptor complex that mediates microglial responses to peptides that accumulate in prion disease (PrP82-146), AD (amyloid-β (Aβ)42) and PD (α-synuclein (αSN)).

Platelet-activating factor antagonists enhance intracellular degradation of amyloid-β42 in neurons via regulation of cholesterol ester hydrolases.

Introduction: The progressive dementia that is characteristic of Alzheimer's disease is associated with the accumulation of amyloid-beta (Aβ) peptides in extracellular plaques and within neurons. Aβ peptides are targeted to cholesterol-rich membrane micro-domains called lipid rafts. Observations that many raft proteins undertake recycling pathways that avoid the lysosomes suggest that the accumulation of Aβ in neurons may be related to Aβ targeting lipid rafts.

Inhibition of phospholipase A2 increased the removal of the prion derived peptide PrP82-146 from cultured neurons.

The prion diseases are characterised by the formation of the disease-associated isoform of the prion protein (PrP(Sc)) and the production of disease-related peptides. The prion derived peptide PrP82-146 bound readily to cortical neurons and was found within detergent resistant membranes that are commonly called lipid rafts. It was not found within lysosomes and the slow degradation of PrP82-146 resulted in a half-life of approximately 5 days.