A cub and sushi domain-containing protein with esterase-like activity confers insecticide resistance in the Indian malaria vector Anopheles stephensi

被引：0

作者：

Kumar, Jatin ^{[1
,2
]}

Kumar, Ankit ^{[3
]}

Gupta, Yash ^{[4
]}

Vashisht, Kapil ^{[1
]}

Kumar, Shivam ^{[5
]}

Sharma, Arvind ^{[1
]}

Kumar, Raj ^{[6
]}

Sharon, Ashoke ^{[5
]}

Tripathi, Praveen K. ^{[1
]}

Das, Ram ^{[1
]}

Singh, Om Prakash ^{[1
]}

Singh, Shailja ^{[6
]}

Chakraborti, Soumyananda ^{[1
,2
]}

Sunil, Sujatha ^{[3
]}

Pandey, Kailash C. ^{[1
,2
,6
]}

机构：

[1] Natl Inst Malaria Res, ICMR, New Delhi, India

[2] Acad Sci & Innovat Res AcSIR, Ghaziabad, Uttar Pradesh, India

[3] Int Ctr Genet Engn & Biotechnol, New Delhi, India

[4] Penn State Coll Med, Dept Med, Hershey, PA USA

[5] Birla Inst Technol Mesra, Dept Chem, Ranchi, Jharkhand, India

[6] Jawaharlal Nehru Univ, Special Ctr Mol Med, New Delhi, India

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2024年 / 300卷 / 10期

关键词：

CULEX-QUINQUEFASCIATUS; PHYLOGENETIC ANALYSIS; CARBOXYLESTERASES;

D O I：

10.1016/j.jbc.2024.107759

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chemical insecticides (organophosphates and pyrethroids) in the form of IRS (Indoor Residual Sprays) and LLINs (Long Lasting Insecticidal Nets) are the cornerstone for vector control, globally. However, their incessant use has resulted in widespread development of resistance in mosquito vectors, warranting continuous monitoring and investigation of the underlying mechanisms of resistance. Here, we identified a previously uncharacterized- Cub and Sushi Domain containing Insecticide Resistance (CSDIR) protein and generated evidence for its role in mediating insecticide resistance in the Anopheles stephensi. A strong binding affinity of the CSDIR protein towards different classes of insecticide molecules-malathion (K-D 6.43 mu M) and deltamethrin (K-D 46.7 mu M) were demonstrated using MD simulation studies and Surface Plasmon Resonance (SPR) experiments. Further, the recombinant CSDIR913-1190 protein exhibited potent esterase-like activity (alpha-naphthyl acetate (alpha-NA)- 1.356 +/- 0.262 mM/min/mg and beta-naphthyl acetate (beta -NA)- 1.777 +/- 0.220 mM/min/mg). Interestingly, dsRNA-mediated gene silencing of the CSDIR transcripts caused >60% mortality in resistant An. stephensi upon 1-h exposure to deltamethrin and malathion insecticides, compared to the control group. A significant reduction in the esterase-like activity was also observed against alpha-NA (p = 0.004) and beta-NA (p = 0.025) in CSDIR silenced mosquitoes compared to the control group. Using computational analysis and experimental data, our results provided significant evidence of the involvement of the CSDIR protein in mediating insecticide resistance in Anopheles mosquitoes. Thereby making the CSDIR protein, a novel candidate for exploration of novel insecticide molecules. These data would also be helpful in further understanding the development of metabolic resistance by the Anopheles vector.

引用

页数：15