Work Package 3: Improving insecticide delivery

LSTM logo NIMR (1) University of Crete CNRFP Logo CNRS  UWA

 

WP3 TeamWork Package Leader:  Dr Gareth Lycett. LSTM

Objectives:

Identify the key behavioural and physiological factors influencing the delivery of pyrethroid insecticides from the impregnated surfaces to the target site in the central nervous system of the mosquito

 

 

 

 

 

 

 

Tasks 

 Progress & Plans 

 

Develop a state of the art system for recording mosquito movement that can be used to determine precise models of mosquito interaction with insecticide treated surfaces

 

 

A functional sensor for recording micro behaviour of individual mosquitoes feeding through a bednet or resting on a solid surface has been developed and is in routine use at LSTM. The 2D system can visualise and track plots of individual mosquito movement for statistical analysis. The system for tracking 3D movement is being used by AvecNet PhD candidate Josie Parker and NIMR scientists to gather experimental data in Tanzania.

The study will generate long-awaited fundamental information on movement and resting behaviour of malaria vectors inside African homes, with or without insecticide or other vector control treatments. This information is likely to lead to innovative designs for new vector control tools.

NT

CS

Identify the physio-chemical and biological barriers to insecticide transport in vivo: Identification of the key barriers that reduce the amount of insecticide that reaches its target site in the insect nervous system 

 

Insecticides have to penetrate the mosquito exoskeleton, travel through the ‘blood’ and cross a layer of cells protecting the nerve tissue (the blood brain barrier) before they can exert their toxic effect.  Each of these points represents a barrier to insecticide uptake and hence to the potency of the insecticide.  We are defining these barriers in the anticipation that this knowledge will lead to improvements in insecticide formulations that may help deliver higher doses of insecticide directly to the insect target site.

Work so far has focused on comparing the cuticular structure between insecticide susceptible and resistant mosquitoes, identifying key transporter proteins (from the ABC family) that are differentially expresses in resistant mosquitoes, and in identifying component of the blood brain barrier.

This work will identify factors that influence the toxicity of pyrethroids to mosquitoes with the aim of assisting the development of insecticide formulations with greater specificity and potency to mosquitoes.

 NT

Develop in vitro assays and structural models to screen novel insecticide preparations: Development of assays to screen for inhibitors of insecticide metabolism

 

We have identified a number of mosquito detoxification enzymes that are produced at elevated levels in multiple insecticide resistant strains and are able to metabolise insecticides in vitro. We have developed alternative in vitro expression systems for these enzymes enabling us to produce each in bulk, and determine their activity against different classes of public health insecticides. 

Via this process we have identified cytochrome P450 enzymes that are able to metabolise multiple insecticide classes. Mosquito populations containing elevated activities of these enzymes are present in the field and are a major concern for resistance management. 

By developing a panel of these enzymes, and making these available to industrial partners, we are providing invaluable tools for the early stage screening of new insecticide leads, aiding the development piepleine 

Trans

NT

 

Publications & Outputs

Victoria A. Ingham, Patricia Pignatelli, Jonathan D. Moore, Simon Wagstaff and Hilary Ranson. The transcription factor Maf-Sregulates metabolic resistance to insecticides in the malaria vector Anopheles gambiae. BMC Genomics 2017 18:669

C Yunta Yanes, N Grisales, K Hemmings, P Pignatelli, H Ranson and M.J. Paine. Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance in An. gambiae. Science Direct, Volume 78, Nov 2016, Pages 50-57

V Balabanidou, N Kambouraki, M Maclean, GL Blomquist, C Tittiger, MP Juarez, SJ Mijailovsky, G Chalepakis, A Anthousi, A Lynd, H Ranson, G Lyccett, J Vontas. Cytochrome P450 associated with insecticide resistance catalyzes cuticular hydrocarbon production in Anopheles gambiae. PNAS, Volume 113, number 33, 9268-9273

N. C. Angarita-Jaimes; J. E. A. Parker; M. Abe; F. Mashauri; J. Martine; C. E. Towers; P. J. McCall; D. P. Towers. A novel video-tracking system to quantify the behaviour of nocturnal mosquitoes attacking human hosts in the field. Journal of The Royal Society April 2016 Volume 13, issue 117

J. E. A. Parker; N. Angarita-Jaimes; M. Abe; C. E. Towers; D. Towers and P. J. McCall. Infrared video tracking of Anopheles gambiae at insecticide-treated bed nets reveals rapid decisive impact after brief localised net contact. Scientific Reports 5, Article number: 13392 (2015)

V. A. Ingham; C. M. Jones; P. Pignatelli; V. Balabanidou; J. Vontas; S. C. Wagstaff; J. D. Moore and H. Ranson. Dissecting the organ specificity of insecticide resistance candidate genes in Anopheles gambiae: known and novel candidate genes. BMC Genomics 2014, 15:1018

A. Chandor-Proust; J. Bibby; M. Régent-Kloeckner; J. Roux; E. Guittard-Crilat; R. Poupardin; M. Asam-Riaz; M. J. Ingraham-Paine; C. Dauphin-Villemant; S. Reynaud and J. P. David. The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling. Biochemical Journal. 2013 455 (75–85)

J. P. David; H. M. Ismail; A. Chandor-Proust and M. J. Ingraham- PaineRole of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth. Philosophical Transactions of the Royal Society B: Biological Sciences. 2013 1612 / 368