scholarly journals Correction: Cytochrome P450 metabolic resistance (CYP6P9a) to pyrethroids imposes a fitness cost in the major African malaria vector Anopheles funestus

Heredity ◽  
2020 ◽  
Vol 125 (5) ◽  
pp. 371-371 ◽  
Author(s):  
Magellan Tchouakui ◽  
Jacob Riveron Miranda ◽  
Leon M. J. Mugenzi ◽  
Doumani Djonabaye ◽  
Murielle J. Wondji ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Malaria Vector ◽  
Anopheles Funestus ◽  
Fitness Cost ◽  
Metabolic Resistance

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Cytochrome P450 metabolic resistance (CYP6P9a) to pyrethroids imposes a fitness cost in the major African malaria vector Anopheles funestus

Heredity ◽  
2020 ◽  
Vol 124 (5) ◽  
pp. 621-632 ◽  
Author(s):  
Magellan Tchouakui ◽  
Jacob Riveron Miranda ◽  
Leon M. J. Mugenzi ◽  
Doumani Djonabaye ◽  
Murielle J. Wondji ◽  
...  
Keyword(s):  
Malaria Vector ◽  
Management Strategy ◽  
Management Strategies ◽  
Resistance Management ◽  
Anopheles Funestus ◽  
Fitness Cost ◽  
Malaria Vectors ◽  
Hybrid Strain ◽  
Metabolic Resistance ◽  
The Impact

Abstract Metabolic resistance threatens the sustainability of pyrethroid-based malaria control interventions. Elucidating the fitness cost and potential reversal of metabolic resistance is crucial to design suitable resistance management strategies. Here, we deciphered the fitness cost associated with the CYP6P9a (P450-mediated metabolic resistance) in the major African malaria vector Anopheles funestus. Reciprocal crosses were performed between a pyrethroid susceptible (FANG) and resistant (FUMOZ-R) laboratory strains and the hybrid strains showed intermediate resistance. Genotyping the CYP6P9a-R resistance allele in oviposited females revealed that CYP6P9a negatively impacts the fecundity as homozygote susceptible mosquitoes (CYP6P9a-SS) lay more eggs than heterozygote (OR = 2.04: P = 0.01) and homozygote resistant mosquitoes. CYP6P9a also imposes a significant fitness cost on the larval development as homozygote resistant larvae (CYP6P9a-RR) developed significantly slower than heterozygote and homozygote susceptible mosquitoes (χ2 = 11.2; P = 0.0008). This fitness cost was further supported by the late pupation of homozygote resistant than susceptible mosquitoes (OR = 2.50; P < 0.01). However, CYP6P9a does not impact the longevity as no difference was observed in the life span of mosquitoes with different genotypes (χ2 = 1.6; P = 0.9). In this hybrid strain, a significant decrease of the resistant CYP6P9a-RR genotype was observed after ten generations (χ2 = 6.6; P = 0.01) suggesting a reversal of P450-based resistance in the absence of selection. This study shows that the P450-mediated metabolic resistance imposes a high fitness cost in malaria vectors supporting that a resistance management strategy based on rotation could help mitigate the impact of such resistance.

scholarly journals Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa Is Driven by Metabolic Resistance Mechanisms

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110058 ◽  
Author(s):  
Charles Mulamba ◽  
Jacob M. Riveron ◽  
Sulaiman S. Ibrahim ◽  
Helen Irving ◽  
Kayla G. Barnes ◽  
...  
Keyword(s):  
East Africa ◽  
Malaria Vector ◽  
Anopheles Funestus ◽  
Resistance Mechanisms ◽  
Metabolic Resistance ◽  
Ddt Resistance ◽  
Major Malaria Vector

scholarly journals Exploring the Mechanisms of Multiple Insecticide Resistance in a Highly Plasmodium-Infected Malaria Vector Anopheles funestus Sensu Stricto from Sahel of Northern Nigeria

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 454
Author(s):  
Sulaiman S. Ibrahim ◽  
Muhammad M. Mukhtar ◽  
Helen Irving ◽  
Jacob M. Riveron ◽  
Amen N. Fadel ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Malaria Vector ◽  
Anopheles Funestus ◽  
Indoor Residual Spraying ◽  
Sensu Stricto ◽  
Bed Nets ◽  
Metabolic Resistance ◽  
Biting Rate ◽  
Insecticide Treated Bed Nets ◽  
Sahel Region

The Nigerian Government is scaling up the distribution of insecticide-treated bed nets for malaria control, but the lack of surveillance data, especially in the Sudan/Sahel region of the country, may hinder targeting priority populations. Here, the vectorial role and insecticide resistance profile of a population of a major malaria vector Anopheles funestus sensu stricto from Sahel of Nigeria was characterised. An. funestus s.s. was the only vector found, with a high human blood index (100%) and a biting rate of 5.3/person/night. High Plasmodium falciparum infection was discovered (sporozoite rate = 54.55%). The population is resistant to permethrin (mortality = 48.30%, LT50 = 65.76 min), deltamethrin, DDT (dichlorodiphenyltrichloroethane) and bendiocarb, with mortalities of 29.44%, 56.34% and 54.05%, respectively. Cone-bioassays established loss of efficacy of the pyrethroid-only long-lasting insecticidal nets (LLINs); but 100% recovery of susceptibility was obtained for piperonylbutoxide (PBO)-containing PermaNet®3.0. Synergist bioassays with PBO and diethyl maleate recovered susceptibility, implicating CYP450s (permethrin mortality = 78.73%, χ2 = 22.33, P < 0.0001) and GSTs (DDT mortality = 81.44%, χ2 = 19.12, P < 0.0001). A high frequency of 119F GSTe2 mutation (0.84) was observed (OR = 16, χ2 = 3.40, P = 0.05), suggesting the preeminent role of metabolic resistance. These findings highlight challenges associated with deployment of LLINs and indoor residual spraying (IRS) in Nigeria.

scholarly journals Influence of GST- and P450-based metabolic resistance to pyrethroids on blood feeding in the major African malaria vector Anopheles funestus

2020 ◽  
Author(s):  
Lynda Nouage ◽  
Emmanuel Elanga-Ndille ◽  
Achille Binyang ◽  
Magellan Tchouakui ◽  
Tatiane Atsatse ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Malaria Vector ◽  
Resistance Genes ◽  
Blood Meal ◽  
Anopheles Funestus ◽  
Blood Feeding ◽  
Meal Size ◽  
Metabolic Resistance ◽  
Feeding Success ◽  
Blood Meal Size

AbstractInsecticide resistance genes are often associated with pleiotropic effects on various mosquito life-history traits. However, very little information is available on the impact of insecticide resistance, especially metabolic resistance, on blood feeding process in mosquitoes. Here, using two recently detected DNA-based metabolic markers in the major malaria vector, An. funestus, we investigated how metabolic resistance genes could affect blood meal intake.After allowing both field F1 and lab F8 Anopheles funestus strains to feed on human arm for 30 minutes, we assessed the association between key parameters of blood meal process including, probing time, feeding duration, blood feeding success and blood meal size, and markers of glutathione S-transferase (L119F-GSTe2) and cytochrome P450 (CYP6P9a_R) - mediated metabolic resistance. None of the parameters of blood meal process was associated with L119F-GSTe2 genotypes. In contrast, for CYP6P9a_R, homozygote resistant mosquitoes were significantly more able to blood-feed than homozygote susceptible (OR = 3.3; CI 95%: 1.4-7.7; P =0.01) mosquitoes. Moreover, the volume of blood meal ingested by CYP6P9a-SS mosquitoes was lower than that of CYP6P9a-RS (P<0.004) and of CYP6P9a-RR (P<0.006). This suggests that CYP6P9a gene affects the feeding success and blood meal size of An. funestus. However, no correlation was found in the expression of CYP6P9a and that of genes encoding for salivary proteins involved in blood meal process.This study suggests that P450-based metabolic resistance may increase the blood feeding ability of malaria vectors and potential impacting their vectorial capacity.

scholarly journals A cytochrome P450 allele confers pyrethroid resistance on a major African malaria vector, reducing insecticide-treated bednet efficacy

2019 ◽  
Vol 11 (484) ◽  
pp. eaat7386 ◽  
Author(s):  
Gareth D. Weedall ◽  
Leon M. J. Mugenzi ◽  
Benjamin D. Menze ◽  
Magellan Tchouakui ◽  
Sulaiman S. Ibrahim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Insecticide Resistance ◽  
Malaria Vector ◽  
Southern Africa ◽  
Malaria Control ◽  
Pyrethroid Resistance ◽  
Mosquito Vector ◽  
Metabolic Resistance ◽  
Pyrethroid Insecticides ◽  
The Impact

Metabolic resistance to insecticides such as pyrethroids in mosquito vectors threatens control of malaria in Africa. Unless it is managed, recent gains in reducing malaria transmission could be lost. To improve monitoring and assess the impact of insecticide resistance on malaria control interventions, we elucidated the molecular basis of pyrethroid resistance in the major African malaria vector, Anopheles funestus. We showed that a single cytochrome P450 allele (CYP6P9a_R) in A. funestus reduced the efficacy of insecticide-treated bednets for preventing transmission of malaria in southern Africa. Expression of key insecticide resistance genes was detected in populations of this mosquito vector throughout Africa but varied according to the region. Signatures of selection and adaptive evolutionary traits including structural polymorphisms and cis-regulatory transcription factor binding sites were detected with evidence of selection due to the scale-up of insecticide-treated bednet use. A cis-regulatory polymorphism driving the overexpression of the major resistance gene CYP6P9a allowed us to design a DNA-based assay for cytochrome P450–mediated resistance to pyrethroid insecticides. Using this assay, we tracked the spread of pyrethroid resistance and found that it was almost fixed in mosquitoes from southern Africa but was absent from mosquitoes collected elsewhere in Africa. Furthermore, a field study in experimental huts in Cameroon demonstrated that mosquitoes carrying the resistance CYP6P9a_R allele survived and succeeded in blood feeding more often than did mosquitoes that lacked this allele. Our findings highlight the need to introduce a new generation of insecticide-treated bednets for malaria control that do not rely on pyrethroid insecticides.

scholarly journals Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
C. L. Moyes ◽  
R. S. Lees ◽  
C. Yunta ◽  
K. J. Walker ◽  
K. Hemmings ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Binding Affinity ◽  
Malaria Vector ◽  
Pyrethroid Resistance ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
Type I ◽  
Cytochrome P450 Enzymes ◽  
Metabolic Resistance ◽  
The Common

Abstract Background It is important to understand whether the potential impact of pyrethroid resistance on malaria control can be mitigated by switching between different pyrethroids or whether cross-resistance within this insecticide class precludes this approach. Methods Here we assess the relationships among pyrethroids in terms of their binding affinity to, and depletion by, key cytochrome P450 enzymes (hereafter P450s) that are known to confer metabolic pyrethroid resistance in Anopheles gambiae (s.l.) and An. funestus, in order to identify which pyrethroids may diverge from the others in their vulnerability to resistance. We then investigate whether these same pyrethroids also diverge from the others in terms of resistance in vector populations. Results We found that the type I and II pyrethroids permethrin and deltamethrin, respectively, are closely related in terms of binding affinity to key P450s, depletion by P450s and resistance within vector populations. Bifenthrin, which lacks the common structural moiety of most pyrethroids, diverged from the other pyrethroids tested in terms of both binding affinity to key P450s and depletion by P450s, but resistance to bifenthrin has rarely been tested in vector populations and was not analysed here. Etofenprox, which also lacks the common structural moiety of most pyrethroids, diverged from the more commonly deployed pyrethroids in terms of binding affinity to key P450s and resistance in vector populations, but did not diverge from these pyrethroids in terms of depletion by the P450s. The analysis of depletion by the P450s indicated that etofenprox may be more vulnerable to metabolic resistance mechanisms in vector populations. In addition, greater resistance to etofenprox was found across Aedes aegypti populations, but greater resistance to this compound was not found in any of the malaria vector species analysed. The results for pyrethroid depletion by anopheline P450s in the laboratory were largely not repeated in the findings for resistance in malaria vector populations. Conclusion Importantly, the prevalence of resistance to the pyrethroids α-cypermethrin, cyfluthrin, deltamethrin, λ-cyhalothrin and permethrin was correlated across malaria vector populations, and switching between these compounds as a tool to mitigate against pyrethroid resistance is not advised without strong evidence supporting a true difference in resistance.

Over expression of a Cytochrome P450 (CYP6P9) in a Major African Malaria Vector, Anopheles Funestus, Resistant to Pyrethroids

2008 ◽  
Vol 17 (1) ◽  
pp. 19-25 ◽  
Author(s):  
D. A. Amenya ◽  
R. Naguran ◽  
T.-C. M. Lo ◽  
H. Ranson ◽  
B. L. Spillings ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Malaria Vector ◽  
Anopheles Funestus ◽  
Over Expression

scholarly journals Evidence of Insecticide Resistance to Pyrethroids and Bendiocarb in Anopheles funestus from Tsararano, Marovoay District, Madagascar

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Tsiriniaina Rakotondranaivo ◽  
Solohery Fanomezana Randriamanarivo ◽  
Mihajarilala Rakotoniaina Tanjona ◽  
Inès Vigan-Womas ◽  
Milijaona Randrianarivelojosia ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Insecticide Resistance ◽  
Resistance Mechanism ◽  
Anopheles Funestus ◽  
Indoor Residual Spraying ◽  
Enzymatic Activities ◽  
Eastern Coast ◽  
Bed Nets ◽  
Metabolic Resistance ◽  
Central Highland

Introduction. In Madagascar, malaria control relies on the countrywide use of long lasting insecticide treated bed nets (LLINs) and on indoor residual spraying (IRS) in the central highland area as well as a small area on the eastern coast. We tested insecticide resistance mechanisms of Anopheles funestus from Tsararano, a malaria endemic village in the coastal health district of Marovoay. Methods. Insecticide susceptibility bioassays were done in July 2017 on first-generation Anopheles funestus (F1) to assess (i) the susceptibility to permethrin (0.05%), deltamethrin (0.05%), DDT (4%), malathion (5%), fenitrothion (1%), and bendiocarb (0.1%); (ii) the effect of preexposure to the piperonyl butoxide (PBO) synergist; and (iii) the enzymatic activities of cytochrome P450, esterases, and glutathione S-transferases (GST). Results. Our results demonstrated that An. funestus was phenotypically resistant to pyrethroids and bendiocarb, with a mortality rate (MR) of 33.6% (95%CI: 24.5-43.7%) and 86% (95%CI: 77.6-92.1%), respectively. In contrast, An. funestus were 100% susceptible to DDT and organophosphates (malathion and fenitrothion). Preexposure of An. funestus to PBO synergist significantly restored the susceptibility to bendiocarb (MR=100%) and increased the MR in the pyrethroid group, from 96% (95%CI: 90.0-98.9%) to 100% for deltamethrin and permethrin, respectively (χ2 = 43, df = 3, P< 0.0001). Enzymatic activities of cytochrome P450 and α-esterases were significantly elevated among An. funestus compared with the IPM reference strain (Mann-Whitney U= 30, P<0.0001; U = 145.5, P <0.0001, respectively). No significant differences of β-esterases activities compared to the IPM reference strain were observed (Mann-Whitney U = 392.5, P = 0.08). Conclusion. In Tsararano, despite the absence of an IRS programme, there is evidence of high levels of insecticide resistance to pyrethroids and bendiocarb in An. funestus. Biochemical data indicated that a metabolic resistance mechanism through the cytochrome P450 genes is operating in the An. funestus population.

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