Mosquito-borne diseases, particularly malaria, remain a major global health challenge. Among different mosquitoes, Anopheles are solely responsible for malaria. Insecticide-based interventions such as insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are central to mosquito control. However, the widespread emergence of insecticide resistance, especially to pyrethroids, the most commonly used insecticides for mosquito worldwide, threatens their effectiveness. While genetic and metabolic mechanisms of resistance are well characterized, behavioral and sequestration-based mechanisms, particularly those involving chemosensory proteins (CSPs), are less understood. CSPs and odorant-binding proteins (OBPs) are integral components of the mosquito olfactory system, mediating host-seeking and other behavioral processes by transporting odorant molecules to olfactory receptors. Recent evidence suggests that CSPs may also bind insecticides like pyrethroids, contributing to resistance through sequestration. In this study, we investigated the structural and functional roles of CSPs in Anopheles mosquitoes. We determined three high-resolution X-ray crystal structures (apo-form) of CSPs (<2 Å) from Anopheles culicifacies and Anopheles gambiae, representing the first crystal structures of CSPs from any Anopheles species reported to date. Using structural, biophysical and computational approaches, we assessed CSP-ligand recognition of various insecticides, specifically pyrethroids and identified key residues potentially involved in pyrethroid interaction through site-directed mutagenesis. The moderate micromolar binding affinities of deltamethrin and permethrin, compared to other insecticides, support the role of CSPs in pyrethroid sequestration. Our findings offer mechanistic insights into pyrethroid sequestration and provide a foundation for developing novel vector control strategies that target CSP-insecticide interactions to combat pyrethroid resistance.
Shibani Biswas, Y. Manickam, Choong Yeu Khai et al.· ACS Infectious Diseases· 0 citations
Spanning almost six decades (1966–2024), 23 whole-genome sequences of Chandipura virus (CHPV), a neurotropic rhabdovirus associated with acute encephalitis primarily in India, have been analyzed. The virus is believed to be transmitted mainly by Sergentomyia and Phlebotomus sandflies. An epidemiological geographical map was developed showing global CHPV detection in sandflies, district-level human encephalitis reports in India, and sandfly species distribution across the country. This integrated landscape links viral occurrence with vector ecology and outbreak potential. To investigate evolutionary dynamics, we analyzed 23 complete genomes, comprising 5 human-derived isolates from India, 17 sandfly-derived isolates from Senegal and Kenya, and one hedgehog-derived isolate from Nigeria. Phylogenetic reconstruction revealed clear lineage segregation between Indian and African strains, indicating region-specific evolution. Despite this divergence, overall genomic variability remained low. Among all genes, the phosphoprotein exhibited relatively higher variability, while human-derived Indian sequences showed lower genetic diversity than the predominantly sandfly-derived African sequences; however, this comparison is confounded by differences in geography, sampling period, and host origin. Selection pressure analyses indicated predominantly purifying selection across coding regions. Episodic diversification analysis detected adaptive events in structural proteins. In the glycoprotein, all diversification sites (P272H, L424W, K503R) overlapped with predicted B-cell epitopes. In the matrix protein, both sites (K20R, D97N) mapped to predicted B-cell epitope regions. In contrast, among the two diversification sites in the nucleoprotein (N35E, A187V), only A187V overlapped with an epitope, whereas N35E was outside predicted antigenic domains. Collectively, these findings provide a comprehensive evolutionary and epidemiological perspective on CHPV and highlight the urgent need for systematic genomic surveillance to inform future diagnostic, vaccine and public health intervention strategies.
P. Kuri, Amit Sharma· PLoS Neglected Tropical Dise...· 0 citations
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