scholarly journals Analysis of the Knockdown Resistance Locus (kdr) in Anopheles stephensi, An. arabiensis, and Culex pipiens s.l. for Insight Into the Evolution of Target-site Pyrethroid Resistance in Eastern Ethiopia

Author(s):  
Tamar E. Carter ◽  
Araya Gebresilassie ◽  
Shantoy Hansel ◽  
Lambodhar Damodaran ◽  
Callum Montgomery ◽  
...  

The malaria vector, Anopheles stephensi, which is typically restricted to South Asia and the Middle East, was recently detected in the Horn of Africa. Addressing the spread of this vector could involve integrated vector control that considers the status of insecticide resistance of multiple vector species in the region. Previous reports indicate that the knockdown resistance mutations (kdr) in the voltage-gated sodium channel (vgsc) are absent in both pyrethroid-resistant and pyrethroid-sensitive An. stephensi in eastern Ethiopia; however, similar information about other vector species in the same areas is limited. In this study, kdr and the neighboring intron were analyzed in An. stephensi, An. arabiensis, and Culex pipiens s.l. collected between 2016 and 2017 to determine the evolutionary history of kdr in eastern Ethiopia. A sequence analysis revealed that all of Cx. pipiens s.l. (N = 42) and 71.6% of the An. arabiensis (N = 67) carried kdr L1014F, which is known to confer target-site pyrethroid resistance. Intronic variation was only observed in An. stephensi (six segregating sites, three haplotypes), which was previously shown to have no kdr mutations. In addition, no evidence of non-neutral evolutionary processes was detected at the An. stephensi kdr intron, thereby further supporting the target-site mechanism not being a major resistance mechanism in this An. stephensi population. Overall, these results show key differences in the evolution of target-site pyrethroid/dichlorodiphenyltrichloroethane resistance mutations in populations of vector species from the same region. Variations in insecticide resistance mechanism profiles between eastern Ethiopian mosquito vectors may lead to different responses to insecticides used in integrated vector control.

2020 ◽  
Author(s):  
Tamar E. Carter ◽  
Araya Gebresilassie ◽  
Shantoy Hansel ◽  
Lambodhar Damodaran ◽  
Callum Montgomery ◽  
...  

AbstractThe malaria vector, Anopheles stephensi, which is typically restricted to South Asia and the Middle East, was recently detected in the Horn of Africa. Controlling the spread of this vector could involve integrated vector control that considers the status of insecticide resistance of multiple vector species in the region. Previous reports indicate that the knockdown resistance mutations (kdr) in the voltage-gated sodium channel (vgsc) are absent in both pyrethroid resistant and sensitive variants of An. stephensi in east Ethiopia but similar information on other vector species in the same areas is limited. In this study, kdr and the neighboring intron was analyzed in An. stephensi, An. arabiensis, and Culex pipiens s. l. collected in east Ethiopia between 2016 and 2017. Sequence analysis revealed that all of Cx. pipiens s.l. (n = 42) and 71.6% of the An. arabiensis (n=67) carried kdr L1014F known to confer target-site pyrethroid resistance. Intronic variation was only observed in An. stephensi (segregating sites = 6, haplotypes = 3) previously shown to have no kdr mutations. In addition, no evidence of non-neutral evolutionary processes was detected at the An. stephensi kdr intron which further supports target-site mechanism not being a major resistance mechanism in this An. stephensi population. Overall, these results suggest differences in evolved mechanisms of pyrethroid/DDT resistance in populations of vector species from the same region. Variation in insecticide resistance mechanisms in East Ethiopian mosquito vectors highlight possible species or population specific biological factors and distinct environmental exposures that shape their evolution.


Acta Tropica ◽  
2020 ◽  
Vol 203 ◽  
pp. 105294 ◽  
Author(s):  
Nurper Guz ◽  
Naciye Sena Cagatay ◽  
Emmanouil A Fotakis ◽  
Enver Durmusoglu ◽  
John Vontas

2021 ◽  
Author(s):  
Yang Xu ◽  
Yang Zhou ◽  
Xixi Li ◽  
Lei Ma ◽  
Dan Zhou ◽  
...  

Abstract The cuticle protein (CP) encoded by CPR63 plays a role in deltamethrin resistance in Culex pipiens pallens. Herein, we investigated the distribution of CPR63 transcripts in this organism, and revealed high expression levels in legs and wings. Furthermore, expression of CPR63 in the legs of deltamethrin-resistant (DR) strains were 1.79-fold higher than in deltamethrin-susceptible (DS) strains. Cuticle analysis of small interfering RNA (siRNA) groups by scanning electron microscopy (SEM) revealed a significantly thinner procuticle of the tarsi in the siCPR63 group than the siNC (negative control (group). Transmission electron microscopy (TEM) revealed that the procuticle, exocuticle and endocuticle thickness of the tarsi were significantly thinner in the siCPR63 group than the siNC group. Our results illuminate the resistance mechanism of CPRs and demonstrate that CPR63 contributes to the resistance phenotype by thickening the cuticle and substantially reducing uptake of insecticides.


Author(s):  
Yuyan Wu ◽  
Qinmei Liu ◽  
Yunpeng Qi ◽  
Yinping Wu ◽  
Qinxiang Ni ◽  
...  

Aedes albopictus is the only vector that can transmit the dengue virus in Zhejiang Province, central China, and it can develop insecticide resistance due to long-term exposure to pyrethroids. The presence of knockdown resistance (kdr) mutations is one of the mechanisms responsible for pyrethroid resistance, and has been reported in some Ae. albopictus populations in southern China. However, little is known about the DNA diversity of the voltage-gated sodium channel (VGSC) gene in Ae. albopictus populations in central China. Four Ae. albopictus field populations were collected, in Yiwu (YW), Quzhou (QZ), Wenzhou (WZ), and Jiaxing (JX) from Zhejiang Province, central China. The susceptibility of Ae. albopictus adults to three pyrethroids (beta-cypermethrin, deltamethrin, and permethrin) was tested using the WHO tube assay, and Kdr mutations were identified via PCR and sequencing. The relationship between kdr mutations and pyrethroid phenotypes was also analyzed. Of the four populations, none was sensitive to any pyrethroid tested, and the YW population showed the strongest pyrethroid resistance. Non-synonymous kdr mutations were detected in codons 1532 and 1534, domain III. At codon 1534, one mutant allele, TCC(S), was detected in the four populations with a frequency of 42.08%, while at codon 1532, one mutant allele, ACC(T), was detected in the JX and QZ populations, with frequencies of 4.22 and 3.03%, respectively. The F1534S mutant allele was positively correlated with both beta-cypermethrin and deltamethrin resistance phenotypes (OR > 1, P < 0.05), whereas the I1532T mutant allele was possibly negatively correlated with beta-cypermethrin, deltamethrin, and permethrin resistance phenotypes (OR < 1, P > 0.05). In conclusion, resistance and resistance mutations regarding to three pyrethroids are already present in the Ae. Albopictus populations from Zhejiang, central China, which prompts the need to use non-insecticide-based methods of insect control.


2019 ◽  
Vol 25 (12) ◽  
pp. 905-913 ◽  
Author(s):  
Ommer Dafalla ◽  
Adel Alsheikh ◽  
Waheed Mohammed ◽  
Khalid Shrwani ◽  
Feras Alsheikh ◽  
...  

PLoS Genetics ◽  
2021 ◽  
Vol 17 (6) ◽  
pp. e1009606
Author(s):  
Karla Saavedra-Rodriguez ◽  
Corey L. Campbell ◽  
Saul Lozano ◽  
Patricia Penilla-Navarro ◽  
Alma Lopez-Solis ◽  
...  

Pyrethroids are one of the few classes of insecticides available to control Aedes aegypti, the major vector of dengue, chikungunya, and Zika viruses. Unfortunately, evolving mechanisms of pyrethroid resistance in mosquito populations threaten our ability to control disease outbreaks. Two common pyrethroid resistance mechanisms occur in Ae. aegypti: 1) knockdown resistance, which involves amino acid substitutions at the pyrethroid target site—the voltage-gated sodium channel (VGSC)—and 2) enhanced metabolism by detoxification enzymes. When a heterogeneous population of mosquitoes is exposed to pyrethroids, different responses occur. During exposure, a proportion of mosquitoes exhibit immediate knockdown, whereas others are not knocked-down and are designated knockdown resistant (kdr). When these individuals are removed from the source of insecticide, the knocked-down mosquitoes can either remain in this status and lead to dead or recover within a few hours. The proportion of these phenotypic responses is dependent on the pyrethroid concentration and the genetic background of the population tested. In this study, we sequenced and performed pairwise genome comparisons between kdr, recovered, and dead phenotypes in a pyrethroid-resistant colony from Tapachula, Mexico. We identified single-nucleotide polymorphisms (SNPs) associated with each phenotype and identified genes that are likely associated with the mechanisms of pyrethroid resistance, including detoxification, the cuticle, and insecticide target sites. We identified high association between kdr and mutations at VGSC and moderate association with additional insecticide target site, detoxification, and cuticle protein coding genes. Recovery was associated with cuticle proteins, the voltage-dependent calcium channel, and a different group of detoxification genes. We provide a list of detoxification genes under directional selection in this field-resistant population. Their functional roles in pyrethroid metabolism and their potential uses as genomic markers of resistance require validation.


2020 ◽  
Vol 57 (6) ◽  
pp. 1830-1834
Author(s):  
Ronald Maestre-Serrano ◽  
Juan Lara-Cobos ◽  
Doris Gomez-Camargo ◽  
Gustavo Ponce-Garcia ◽  
Paula Pareja-Loaiza ◽  
...  

Abstract The use of insecticides for the control of Aedes aegypti (L.) (Diptera: Culicidae) in Colombia has indirectly influenced the susceptibility status of Culex quinquefasciatus Say populations. We evaluated pyrethroid susceptibility in two populations of Cx. quinquefasciatus in the Atlantico Department of Colombia and its possible resistance mechanism (kdr mutation). Bottle bioassays were performed for permethrin, deltamethrin, and λ-cyhalothrin in female mosquitoes of Cx. quinquefasciatus. The resistance ratios (RRs) for KC50 and LC50 for each insecticide in the field populations examined were determined, using the Cartagena strain as the susceptible control. The L1014F kdr mutation was identified in the para gene of the voltage-gated sodium channel (vgsc), along with its allelic and genotypic frequency. Low knockdown resistance (RRKC50) to deltamethrin was found in Puerto Colombia and Soledad populations as well as low resistance to λ-cyalothrin in this latter population. Moderate knockdown resistance to permethrin was found in both populations. At 24 h post-exposure on the other hand, there was low resistance (RRLC50) to permethrin in Puerto Colombia and moderate resistance in Soledad. Moderate resistance to deltamethrin was found in Puerto Colombia and low resistance in Soledad. Low resistance to λ-cyhalothrin was seen in Puerto Colombia and moderate resistance in Soledad. Variability was found in the susceptibility to the pyrethroids in the populations of Cx. quinquefasciatus evaluated, and the L1014F kdr mutation is reported for the first time as a possible pyrethroid resistance mechanism in this species in Colombia.


2021 ◽  
Vol 15 (5) ◽  
pp. e0009393
Author(s):  
Ndeye Marie Sene ◽  
Konstantinos Mavridis ◽  
El Hadji Ndiaye ◽  
Cheikh Tidiane Diagne ◽  
Alioune Gaye ◽  
...  

Aedes aegypti is the main epidemic vector of arboviruses in Africa. In Senegal, control activities are mainly limited to mitigation of epidemics, with limited information available for Ae. aegypti populations. A better understanding of the current Ae. aegypti susceptibility status to various insecticides and relevant resistance mechanisms involved is needed for the implementation of effective vector control strategies. The present study focuses on the detection of insecticide resistance and reveals the related mechanisms in Ae. aegypti populations from Senegal. Bioassays were performed on Ae. aegypti adults from nine Senegalese localities (Matam, Louga, Barkedji, Ziguinchor, Mbour, Fatick, Dakar, Kédougou and Touba). Mosquitoes were exposed to four classes of insecticides using the standard WHO protocols. Resistance mechanisms were investigated by genotyping for pyrethroid target site resistance mutations (V1016G, V1016I, F1534C and S989P) and measuring gene expression levels of key detoxification genes (CYP6BB2, CYP9J26, CYP9J28, CYP9J32, CYP9M6, CCEae3a and GSTD4). All collected populations were resistant to DDT and carbamates except for the ones in Matam (Northern region). Resistance to permethrin was uniformly detected in mosquitoes from all areas. Except for Barkédji and Touba, all populations were characterized by a susceptibility to 0.75% Permethrin. Susceptibility to type II pyrethroids was detected only in the Southern regions (Kédougou and Ziguinchor). All mosquito populations were susceptible to 5% Malathion, but only Kédougou and Matam mosquitoes were susceptible to 0.8% Malathion. All populations were resistant to 0.05% Pirimiphos-methyl, whereas those from Louga, Mbour and Barkédji, also exhibited resistance to 1% Fenitrothion. None of the known target site pyrethroid resistance mutations was present in the mosquito samples included in the genotyping analysis (performed in > 1500 samples). In contrast, a remarkably high (20-70-fold) overexpression of major detoxification genes wasobserved, suggesting that insecticide resistance is mostly mediated through metabolic mechanisms. These data provide important evidence to support dengue vector control in Senegal.


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