Development of genomic resources to determine the genetic basis of insecticide resistance in sandfly vectors

About This Grant

Background: Lutzomyia sandflies are the primary vectors of Leishmania in the neotropics. Leishmania infection manifests as multiple diseases, some of which are lethal. During the past 20 years, the distribution of Leishmania-carrying sandflies has spread, with significant increases in the number of reported cases of leishmaniasis disease (1–6). Given the contemporary geographic range of Lutzomyia sandflies, over 350 million people are at risk of leishmaniasis. Nearly 1.5 million cases are reported annually (1, 3, 5, 7, 8), in what is likely an underestimate of infection burden (7, 9–14). Understanding the processes that lead to genetic and phenotypic variation in sandflies influences the ability to monitor and predict vector spread and control. Aims and Approach: In this proposal, we leverage our expertise to advance sandfly management using integrative analyses of insecticide resistance (IR). We have the necessary permits and facilities to collect and work with sandflies, enabling us to rapidly initiate and efficiently complete the proposed work. Aim 1 will generate pangenome graphs with highly contiguous reference genomes for five vector species. This will enable the detection of loci under selection across sandfly species and establish a sandfly community genomic resource. Aim 2 will build on our preliminary data and expertise ecological and evolutionary genetics to sample natural variation and map alleles associated with pyrethroid resistance – one of the main strategies for controlling sandflies – in Lutzomyia evansi. This work will provide insights into the genetic basis of IR in a genetically understudied disease vector. Long-term goal: Our research program focuses on evolutionary and population genetics in insects. We are now applying our expertise to systems relevant to human health. This proposal launches an integrative research program combining population genomics, lab experimentation, and field sampling to generate genomic resources and foundational knowledge for Lutzomyia sandfly vectors. The outcomes—quantifying IR and identifying its genetic basis—will improve understanding of Lutzomyia adaptation to control strategies. Our preliminary data, necessary permits, and expertise in sampling and analyzing natural variation enable us to efficiently complete the proposed work on time. Health-relatedness: Leishmania disease burden is substantial, with estimates that over 12 million individuals are currently infected (8, 15). This disease burden is projected to grow as global trade, and travel facilitate range expansion of vectoral Lutzomyia species. Identifying genomic regions under selection – and specifically those involved in IR – using innovative approaches contributes significantly toward understanding and ultimately projecting leishmaniasis risk in contemporary and in novel geographical areas as sandfly vector populations continue their expansion toward the US.