Identification of molecular basis of resistance to neurotoxic insecticides in a Chagas vector

• Applicant: Professorin Dr. Victoria Ingham
• Subject Area: Animal Physiology and Biochemistry ; Clinical Infectiology and Tropical Medicine
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 543872932

According to the World Health Organization (WHO), Chagas is a neglected tropical disease that can cause disability and death. Around 7 million people live with Chagas in Latin America, whilst a fifth of the population of this subcontinent are at risk of contracting it. The causative agent of Chagas disease is the protozoan parasite Trypanosoma cruzi which is transmitted by the faeces of hematophagous insects of the triatomine subfamily, as the parasite is deposited on the host’s skin during blood feeding. The main method of controlling the spread of Chagas disease is insecticide-based vector control, through the use of pyrethroid insecticides. Pyrethroid insecticides act on their molecular target, the voltage-gated sodium channel, altering nerve impulse transmission. At adequate doses they are lethal to insects, whilst safe for vertebrates. In Argentina they have been used for decades to control Chagas disease vectors; however, resistance to this class is now widespread, hindering Chagas control. Within this proposal University Hospital Heidelberg and Laboratorio de Neurobiología de Insectos-Centro Regional de Estudios Genómicos will combine expertise in insecticide resistance, imaging, transcriptomics, molecular biology and triatomine biology to determine the molecular basis of resistance with a particular focus on the nervous tissue. To do this, field-caught populations of triatomine bugs with different resistance rates from the regions of Salta and Chaco in Argentina will be studied. Toxicological analyses of polymorphisms associated with resistance in the voltage-dependent sodium channel and quantitative transcriptomics in the nervous system will be carried out to elucidate the molecular basis of resistance. With these results, a group of genes of interest will be chosen for gene silencing experiments and analysis of expression patterns in the nervous system. Additionally, we will design field-diagnostics to track the spread of resistance to this class to inform management strategies. Taken together, this proposal will advance basic biology knowledge on the architecture and changes to the nervous system in a clinically relevant neglected tropical disease vector.

• DFG Programme: Research Grants
• International Connection: Argentina
• Partner Organisation: Consejo Nacional de Investigaciones Científicas y Técnicas
• Cooperation Partner: Dr. Sheila Ons