Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens

Abstract Background Culex pipiens pallens poses a serious threat to human health because of its widespread distribution, high carrier capacity for several arboviruses, frequent human-biting, and growth in urban environments. Pyrethroid insecticides have been mainly used to control adult Cx. pipiens...

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Main Authors: Yang Xu, Xiaoshan Yang, Xiaohong Sun, Xixi Li, Zhihan Liu, Qi Yin, Lei Ma, Dan Zhou, Yan Sun, Bo Shen, Changliang Zhu
Format: Article
Language:English
Published: BMC 2020-10-01
Series:Parasites & Vectors
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13071-020-04383-w
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author Yang Xu
Xiaoshan Yang
Xiaohong Sun
Xixi Li
Zhihan Liu
Qi Yin
Lei Ma
Dan Zhou
Yan Sun
Bo Shen
Changliang Zhu
author_facet Yang Xu
Xiaoshan Yang
Xiaohong Sun
Xixi Li
Zhihan Liu
Qi Yin
Lei Ma
Dan Zhou
Yan Sun
Bo Shen
Changliang Zhu
author_sort Yang Xu
collection DOAJ
description Abstract Background Culex pipiens pallens poses a serious threat to human health because of its widespread distribution, high carrier capacity for several arboviruses, frequent human-biting, and growth in urban environments. Pyrethroid insecticides have been mainly used to control adult Cx. pipiens pallens during outbreaks of mosquito-borne diseases. Unfortunately, mosquitoes have developed resistance, rendering the insecticides ineffective. Cuticular resistance is the primary mechanism of pyrethroid resistance. Previously, we revealed that cuticular protein of low complexity CPLCG5 is a major cuticular protein associated with deltamethrin resistance in Cx. pipiens pallens, which is enriched in the cuticle of mosquitoes’ legs and participates in pyrethroid resistance by forming a rigid matrix. However, the regulatory mechanisms of its transcription remain unknown. Results First, qRT-PCR analysis revealed that the expression of FTZ-F1 (encoding Fushi tarazu-Factor 1) was ~ 1.8-fold higher in the deltamethrin-resistant (DR) than deltamethrin-susceptible (DS) strains at 24 h post-eclosion (PE) and ~ 2.2-fold higher in the DR strain than in the DS strain at 48 h PE. CPLCG5 and FTZ-F1 were co-expressed in the legs, indicating that they might play an essential role in the legs. Dual luciferase reporter assays and EMSA (electrophoretic mobility shift experiments) revealed that FTZ-F1 regulates the transcription of CPLCG5 by binding to the FTZ-F1 response element (− 870/− 864). Lastly, knockdown of FTZ-F1 not only affected CPLCG5 expression but also altered the cuticle thickness and structure of the legs, increasing the susceptibility of the mosquitoes to deltamethrin in vivo. Conclusions The results revealed that FTZ-F1 regulates the expression of CPLCG5 by binding to the CPLCG5 promoter region, altering cuticle thickness and structure, and increasing the susceptibility of mosquitoes to deltamethrin in vivo. This study revealed part of the mechanism of cuticular resistance, providing a deeper understanding of insecticide resistance.
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spelling doaj.art-ab861d94f7f1477aa01e504eabf9a5e82022-12-21T23:36:31ZengBMCParasites & Vectors1756-33052020-10-0113111310.1186/s13071-020-04383-wTranscription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallensYang Xu0Xiaoshan Yang1Xiaohong Sun2Xixi Li3Zhihan Liu4Qi Yin5Lei Ma6Dan Zhou7Yan Sun8Bo Shen9Changliang ZhuDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Blood Transfusion, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityAbstract Background Culex pipiens pallens poses a serious threat to human health because of its widespread distribution, high carrier capacity for several arboviruses, frequent human-biting, and growth in urban environments. Pyrethroid insecticides have been mainly used to control adult Cx. pipiens pallens during outbreaks of mosquito-borne diseases. Unfortunately, mosquitoes have developed resistance, rendering the insecticides ineffective. Cuticular resistance is the primary mechanism of pyrethroid resistance. Previously, we revealed that cuticular protein of low complexity CPLCG5 is a major cuticular protein associated with deltamethrin resistance in Cx. pipiens pallens, which is enriched in the cuticle of mosquitoes’ legs and participates in pyrethroid resistance by forming a rigid matrix. However, the regulatory mechanisms of its transcription remain unknown. Results First, qRT-PCR analysis revealed that the expression of FTZ-F1 (encoding Fushi tarazu-Factor 1) was ~ 1.8-fold higher in the deltamethrin-resistant (DR) than deltamethrin-susceptible (DS) strains at 24 h post-eclosion (PE) and ~ 2.2-fold higher in the DR strain than in the DS strain at 48 h PE. CPLCG5 and FTZ-F1 were co-expressed in the legs, indicating that they might play an essential role in the legs. Dual luciferase reporter assays and EMSA (electrophoretic mobility shift experiments) revealed that FTZ-F1 regulates the transcription of CPLCG5 by binding to the FTZ-F1 response element (− 870/− 864). Lastly, knockdown of FTZ-F1 not only affected CPLCG5 expression but also altered the cuticle thickness and structure of the legs, increasing the susceptibility of the mosquitoes to deltamethrin in vivo. Conclusions The results revealed that FTZ-F1 regulates the expression of CPLCG5 by binding to the CPLCG5 promoter region, altering cuticle thickness and structure, and increasing the susceptibility of mosquitoes to deltamethrin in vivo. This study revealed part of the mechanism of cuticular resistance, providing a deeper understanding of insecticide resistance.http://link.springer.com/article/10.1186/s13071-020-04383-wCulex pipiens pallensDeltamethrinResistanceCuticular proteinCPLCG5Transcription factor
spellingShingle Yang Xu
Xiaoshan Yang
Xiaohong Sun
Xixi Li
Zhihan Liu
Qi Yin
Lei Ma
Dan Zhou
Yan Sun
Bo Shen
Changliang Zhu
Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens
Parasites & Vectors
Culex pipiens pallens
Deltamethrin
Resistance
Cuticular protein
CPLCG5
Transcription factor
title Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens
title_full Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens
title_fullStr Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens
title_full_unstemmed Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens
title_short Transcription factor FTZ-F1 regulates mosquito cuticular protein CPLCG5 conferring resistance to pyrethroids in Culex pipiens pallens
title_sort transcription factor ftz f1 regulates mosquito cuticular protein cplcg5 conferring resistance to pyrethroids in culex pipiens pallens
topic Culex pipiens pallens
Deltamethrin
Resistance
Cuticular protein
CPLCG5
Transcription factor
url http://link.springer.com/article/10.1186/s13071-020-04383-w
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