RT Journal Article
SR Electronic
T1 Comparison of the knockdown resistance locus (<em>kdr</em>) in <em>Anopheles stephensi, An. arabiensis</em>, and <em>Culex pipiens s.l.</em> suggests differing mechanisms of pyrethroid resistance in east Ethiopia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.13.093898
DO 10.1101/2020.05.13.093898
A1 Tamar E. Carter
A1 Araya Gebresilassie
A1 Shantoy Hansel
A1 Lambodhar Damodaran
A1 Callum Montgomery
A1 Victoria Bonnell
A1 Karen Lopez
A1 Daniel Janies
A1 Solomon Yared
YR 2020
UL http://biorxiv.org/content/early/2020/05/14/2020.05.13.093898.abstract
AB The recent detection of the malaria vector mosquito species Anopheles stephensi, which is typically restricted to South Asia and the Middle East, in the Horn of Africa emphasizes the importance of continued vector surveillance in the region. Previous reports of the absence of the knockdown resistance mutations (kdr) in the voltage-gated sodium channel (vgsc) in pyrethroid resistant An. stephensi emphasize the need for further investigation of the kdr-mediated resistance mutations in other mosquitoes of east Ethiopia. In this study, the knockdown resistance locus (kdr) in the voltage gated sodium channel (vgsc) was analyzed in An. stephensi, An. arabiensis, and Culex pipiens s. l. collected in east Ethiopia between 2016 and 2017. A portion of both vsgc was sequenced and amplified in An. arabiensis and Cu. pipiens s.l. and compared with An. stephensi sequences previously generated. All of Cu. pipiens s.l. (n = 42) and 71.6% of the An. arabiensis (n=67) carried kdr L1014F alleles known to confer pyrethroid resistance. Analysis of the downstream kdr intron in all three species revealed nucleotide diversity only in An. stephensi (s = 6, h = 3) previously shown to have no 1014 mutations. In addition, no evidence of non-neutral evolutionary processes was detected for An. stephensi kdr intron. Finally, no association between the An. stephensi kdr intron haplotypes and permethrin or DDT phenotypic resistance was detected. Overall, these results reveal evidence for differing degrees of selection at kdr that may suggest differing mechanisms of resistance across these species. While the presence of the L1014F mutation suggests target-site resistance mechanisms in An. arabiensis and Cu. pipiens in east Ethiopia, the lack of signatures for selection at kdr for resistant and non-resistant An. stephensi does not support a target-site mechanism of resistance based on the kdr locus in An. stephensi. This evidence of differing mechanisms of resistance across vector species can inform the design of future integrated strategies for vector control.Synopsis Growing insecticide resistance hinders efforts to control the spread of vector-borne diseases. This is further complicated with the evidence of vectors moving into new regions as is the case with the newly detected Anopheles stephensi in the Horn of Africa. With this dynamic situation, it is important to evaluate how different local vectors develop resistance to insecticides to improve the implementation of insecticide-based strategies meant to target multiple vectors species. The authors analyzed a known insecticide resistance locus, kdr, in the An. stephensi and long-established An. arabiensis and Culex pipiens sl populations in east Ethiopia for evolutionary signatures of the common mechanism of resistance known as knockdown (target-site) resistance. The authors show that while An. arabiensis and Culex pipiens sl carry evolutionary signatures of the knockdown resistance mechanism, the An. stephensi do not. Additional comparisons of kdr genetic diversity and insecticide resistance status in the An. stephensi from Ethiopia further supports that the kdr and neighboring loci likely do not play a role in resistance in this An. stephensi population. These findings support the notion of that vectors in the same general region can have different modes for which they evolve resistance in east Ethiopia.BLASTBasic Local Alignment Search ToolDNADeoxyribonucleic AcidFMOHFederal Ministry of HealthITS2Internal transcribed spacer 2 regionNCBINational Center of Biotechnology InformationPCRPolymerase chain reactionKDRknockdown resistanceVGSCvoltage-gated sodium channelCOICytochrome c oxidase subunit 1 geneCDCCenters for Disease Control and PreventionWHOWorld Health Organization