Biology subjects

Remadi, L.

Publications and source records attributed to Remadi, L..

4 recordsLinked to original sources

bioRxiv2026

Monitoring insecticide resistance in mosquitoes from Tunisia: implications for vector control strategies

Tunisia is considered a high-risk country for arboviral transmission, and the re-emergence of malaria. Vector control programs predominantly rely on insecticide-based interventions, however knowledge on the insecticide resistance status of local vectors is limited. Here, we determined the mosquito species composition and investigated the resistance status of disease vectors to insecticides, collected from two distinct ecological settings; urban setting and rural setting. Known insecticide resistance loci were molecularly analysed. A total of 210 mosquitoes were collected, representing three main genera: Culex (n = 119), Aedes (n = 79), and Anopheles (n = 1). Within the Culex genus, Cx. pipiens pipiens and Cx. pipiens hybrids were the predominant species in Monastir and Kairouan respectively. Amongst Aedes, Ae. albopictus was the most abundant species in Monastir, while Ae. caspius predominated in Kairouan. The knockdown (kdr) mutation L1014F was detected at both sites across the three Cx. pipiens biotypes. In contrast, Cx. perexiguus showed no kdr mutation in Kairouan and a low frequency in Monastir. Among Aedes species, kdr mutations were detected exclusively in Ae. albopictus, restricted to domain III (mutation I1532T). No mutations in the chs gene were identified in both populations. Aedes albopictus collected in Monastir exhibited a moderate copy number variation for both carboxylesterases 3 and 6. No mutations were detected in the Anopheles labranchia. Our study results indicate the suitability of diflubenzuron for Culex and Ae. albopictus control in central Tunisia, emerging pyrethroid resistance in both vector species, and possibly reduced organophosphate efficacy against Ae. albopictus.

molecular biology↗

bioRxiv2026

Synergistic action of different molecular mechanisms causes striking levels of insecticide resistance in the malaria vector Anopheles gambiae

Intensifying insecticide resistance in the malaria vector Anopheles gambiae poses a serious threat to the hard-won gains in reducing malaria deaths in Africa. The genetic basis of insecticide resistance is often complex, involving multiple genes and mutations. However, we still lack a clear understanding of how each mechanism contributes to overall resistance and how highly resistant phenotypes arise. In this study we generated a suite of transgenic An. gambiae strains carrying either individual mechanisms or combinations that frequently co-occur in nature. We show that co-overexpression of different classes of detoxification enzymes (CYP6P3, CYP6M2, CYP9K1, ABCH2, GSTE2 and COEAE6G), as well as the overexpression of detoxification enzymes in the presence of target site resistance mutations, can lead to substantially greater levels of resistance. Our findings suggest that increased resistance strength is a primary driver for selection of multi-mechanism resistance and are transformative for the scientific insight required to design robust molecular diagnostics for timely and reliable resistance detection in the field. We further show that P450 based resistance can constitute an Achilles heel for highly resistant mosquitoes, making them more vulnerable to pro-insecticides; compounds that typically require P450 activation. Our results advance our understanding of the mechanistic basis of insecticide resistance and have important implications for the design and implementation of effective and evidence-based resistance management strategies.

genetics↗

bioRxiv2026

Mitigating CYP450-Mediated Insecticide Resistance in Malaria Vectors with Cannabis-Derived Synergists: The Potential of Cannabidiol

Insecticide resistance in mosquitoes, largely mediated by cytochrome P450 monooxygenases (CYPs), compromises the efficacy of vector control tools. In this study, chemically-wise selected natural extracts and compounds were screened for their CYP inhibition potential. Among 37 tested plant extracts and fractions, a decarboxylated acidic fraction of industrial hemp (Cannabis sativa Linnaeus var. Futura 75) emerged as a promising hit, and phytochemical profiling identified cannabidiol (CBD) as its major component (IC = 18.37 M for CYP9K1). CBD was used as a scaffold to generate semisynthetic analogues; of which a piperazinyl analogue outperformed the natural scaffold demonstrating significantly greater potency (IC = 2.50 M for CYP9K1). Docking studies using homology-derived CYP9K1 models also supported a stronger binding affinity of the piperazinyl analogue relative to CBD. Toxicity assays using pyrethroid-resistant Anopheles gambiae Giles adults confirmed that neither CBD nor the piperazinyl analogue had intrinsic toxicity, yet the semisynthetic analogue significantly enhanced deltamethrin efficacy, showing a threefold synergistic effect. The safety profile of the cannabis compounds for non-target organisms was evaluated through human cell line cytotoxicity tests and bee toxicity assays, suggesting low non-target organism toxicity. Our study describes the identification of a plant-derived synergist lead with strong potential as an insecticide additive to combat metabolic resistance in malaria-transmitting mosquitoes.

pharmacology and toxicology↗

bioRxiv2024

Development and application of species ID and insecticide resistance assays, for monitoring sand fly Leishmania vectors in the Mediterranean basin and in the Middle East

AbstractsO_ST_ABSBackgroundC_ST_ABSDevelopment of insecticide resistance (IR) in sand fly populations is an upcoming issue of public health concern, threatening leishmaniasis mitigation efforts by insecticide- based vector control. There is a major knowledge gap in the IR status of wild populations worldwide, possibly attributed to the unavailability of specialized tools, such as bioassay protocols, species baseline susceptibility to insecticides and molecular markers, to monitor such phenomena in sand flies. Methodology/ Principal findingsSeveral sand fly populations from (semi-)rural regions of Greece, Turkey and Iran were sampled and identified to species, showing populations structure in accordance with previously reported data. Genotyping of known pyrethroid resistance-associated loci revealed the occurrence of voltage-gated sodium channel (vgsc) mutations in all surveyed countries. Knock-down resistance (kdr) mutation L1014F was prevalent in Turkish regions and L1014F and L1014S were recorded for the first time in Iran and in Turkey and Greece, respectively, yet in low frequencies. Moreover, CDC bottle bioassays against pyrethroids in mixed species populations from Greece indicated full susceptibility, using though the mosquito discriminating doses. In parallel, we established a novel individual bioassay protocol and applied it comparatively among distinct Phlebotomus species populations, to detect any possible divergent species-specific response to insecticides. Indeed, a significantly different knock-down rate between P. simici and P. perfiliewi was observed upon exposure to deltamethrin. Conclusions/SignificanceIR in sand flies is increasingly reported in leishmaniasis endemic regions, highlighting the necessity to generate additional monitoring tools, that could be implemented in relevant eco-epidemiological settings, in the context of IR management. Our molecular and phenotypic data add to the IR map in a macroarea with otherwise limited data coverage. Author SummaryPhlebotomine sand flies vector leishmaniasis to human and animals, a neglected tropical disease of the (sub-)tropics, displaying an expanding epidemiological tendency towards previously non-endemic regions. As leishmaniasis eradication largely relies on vectors insecticidal control, regular monitoring of insecticide resistance (IR) is a core element of integrated vector management. IR data are limited in sand fly populations worldwide though, among others due to the unavailability of robust molecular diagnostic and phenotyping tools. Here, we aim to characterise the pyrethroid resistance (PyR) status of populations originating from countries of the Mediterranean basin and the Middle East; i.e. Greece, Turkey and Iran. PyR-associated mutations were detected in all three countries, while the populations from Greece exhibited susceptibility upon exposure to deltamethrin in CDC bioassays. We established an individual bioassay protocol to enable IR monitoring in settings with multi- species population structure, and applied it comparatively among three distinct Phlebotomus species, revealing that they respond differently to insecticide treatment. Our study will facilitate systematic surveillance and evidence-based sand fly control in the endemic regions.

pharmacology and toxicology↗