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Peer-reviewedCC BY 4.0PLOS Neglected Tropical Diseases

Resistance to pyrethroids in Aedes aegypti: Insights into transcriptomic response to different insecticide concentrations

  1. 1Grupo Biología y Control de Enfermedades Infecciosas – BCEI, Universidad de Antioquia, UdeA, Medellín, Colombia
  2. 2Center for Cell Biology, Development and Disease, Department of Biological Sciences, Simon Fraser University, Burnaby, Canada
  3. 3Colorado State University, Department of Microbiology, Immunology and Pathology, Center of Vector-borne and Infectious Diseases, Fort Collins, Colorado, United States of America

Abstract

Insecticide spraying is a common strategy for controlling dengue outbreaks, but its effectiveness is compromised by the development of resistance in mosquito populations. In this study, we subjected a strain of Aedes aegypti known for its exceptional ability to develop resistance to controlled permethrin and lambda-cyhalothrin insecticides pressure using two different concentrations. We analyzed resistance mechanisms that are enhanced at each concentration and used RNA sequencing to identify transcripts specifically associated with these exposure levels. Our objective was to uncover the molecular mechanisms triggered by different insecticide concentrations and to distinguish responses between type I and type II pyrethroids, which differ in chemical structure. Our results showed that kdr mutations confer only moderate levels of resistance, as do detoxifying enzymes. For lambda-cyhalothrin, we identified genes involved in the electron transport chain, mitochondrial function, and overall responses to oxidative stress. tRNA transcripts were also upregulated, along with mitochondrial and stress-response transcripts, suggesting a metabolic shift, particularly toward maintaining homeostasis under oxidative stress. These changes point to mechanisms that sustain resistance to this type II insecticide beyond direct detoxification in this population. On the contrary, permethrin induced marked overexpression of cuticle genes, CYP450 genes (especially CYP4), and Odorant Binding Proteins. These expression patterns, together with metabolic enzymes, point to detoxification, reduced penetration, or even sequestration of insecticide, all of which intensify with increasing concentrations. This overregulation of genes suggests an integrated response complemented by classical metabolic detoxification and accompanied by overregulation of mitochondrial complexes. We showed that despite the shared mode of action of the insecticides permethrin and lambda-cyhalothrin, they elicit distinct responses in this Ae. aegypti population. We also showed that the transcriptomic response depends on insecticide concentration and may modulate insecticide tolerance. This article advances understanding of the complexity of pyrethroid resistance in Aedes aegypti and underscores the importance of considering both the insecticide type and the concentration used in vector control programs. Author summary: Aedes aegypti mosquitoes transmit dengue and other arboviruses, being a major public health problem in tropical regions like Colombia, where control relies on pyrethroid insecticide spraying. Based on reports of inconsistent results in the field due to different effects of insecticide concentrations, we recreated variable doses by exposing a resistant Colombian Aedes aegypti strain to low (LC25) and high (LC75) concentrations of permethrin (type I) and lambda-cyhalothrin (type II) to identify concentration-dependent resistance mechanisms. Using genetic mutation analysis, enzyme activity assays, and RNA sequencing, we identified the molecular mechanisms these mosquitoes use to survive.

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BibTeX
@article{munoz2026resistance,
  title = {{Resistance to pyrethroids in Aedes aegypti: Insights into transcriptomic response to different insecticide concentrations}},
  author = {Alejandro Mejía Muñoz and Ana María Mejía-Jaramillo and Carl Lowenberger and Karla Saavedra-Rodríguez and Omar Triana-Chávez},
  journal = {PLOS Neglected Tropical Diseases},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pntd.0014144},
  url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014144},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Resistance to pyrethroids in Aedes aegypti: Insights into transcriptomic response to different insecticide concentrations
AU  - Alejandro Mejía Muñoz
AU  - Ana María Mejía-Jaramillo
AU  - Carl Lowenberger
AU  - Karla Saavedra-Rodríguez
AU  - Omar Triana-Chávez
PY  - 2026
DA  - 2026/09/24
JO  - PLOS Neglected Tropical Diseases
DO  - 10.1371/journal.pntd.0014144
UR  - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014144
AB  - Insecticide spraying is a common strategy for controlling dengue outbreaks, but its effectiveness is compromised by the development of resistance in mosquito populations. In this study, we subjected a strain of Aedes aegypti known for its exceptional ability to develop resistance to controlled permethrin and lambda-cyhalothrin insecticides pressure using two different concentrations. We analyzed resistance mechanisms that are enhanced at each concentration and used RNA sequencing to identify transcripts specifically associated with these exposure levels. Our objective was to uncover the molecular mechanisms triggered by different insecticide concentrations and to distinguish responses between type I and type II pyrethroids, which differ in chemical structure. Our results showed that kdr mutations confer only moderate levels of resistance, as do detoxifying enzymes. For lambda-cyhalothrin, we identified genes involved in the electron transport chain, mitochondrial function, and overall responses to oxidative stress. tRNA transcripts were also upregulated, along with mitochondrial and stress-response transcripts, suggesting a metabolic shift, particularly toward maintaining homeostasis under oxidative stress. These changes point to mechanisms that sustain resistance to this type II insecticide beyond direct detoxification in this population. On the contrary, permethrin induced marked overexpression of cuticle genes, CYP450 genes (especially CYP4), and Odorant Binding Proteins. These expression patterns, together with metabolic enzymes, point to detoxification, reduced penetration, or even sequestration of insecticide, all of which intensify with increasing concentrations. This overregulation of genes suggests an integrated response complemented by classical metabolic detoxification and accompanied by overregulation of mitochondrial complexes. We showed that despite the shared mode of action of the insecticides permethrin and lambda-cyhalothrin, they elicit distinct responses in this Ae. aegypti population. We also showed that the transcriptomic response depends on insecticide concentration and may modulate insecticide tolerance. This article advances understanding of the complexity of pyrethroid resistance in Aedes aegypti and underscores the importance of considering both the insecticide type and the concentration used in vector control programs. Author summary: Aedes aegypti mosquitoes transmit dengue and other arboviruses, being a major public health problem in tropical regions like Colombia, where control relies on pyrethroid insecticide spraying. Based on reports of inconsistent results in the field due to different effects of insecticide concentrations, we recreated variable doses by exposing a resistant Colombian Aedes aegypti strain to low (LC25) and high (LC75) concentrations of permethrin (type I) and lambda-cyhalothrin (type II) to identify concentration-dependent resistance mechanisms. Using genetic mutation analysis, enzyme activity assays, and RNA sequencing, we identified the molecular mechanisms these mosquitoes use to survive.
SN  - 1935-2735
ER  -