Elucidating biosynthesis of the Lutzomyia longipalpis sandfly pheromone for sustainable production and control of leishmaniasis

Leishmaniases are a group of neglected tropical diseases caused by a protozoan parasite. In Central and South America the disease is spread by the blood-feeding sand fly, Lutzomyia longipalpis and related species. The disease is a particular challenge in Brazil, which has the highest incidence of leishmaniasis. Population control of the Lutzomyia longipalpis fly is a recognised strategy for preventing leishmaniasis. Indiscriminate spraying of insecticide is, however, harmful to all insect fauna: including many beneficial insects, such as pollinators as well as prey for a diverse range of animals. The use of pheromones to attract insects for population monitoring, mass trapping and mating disruption are all established approaches to pest control. Pheromones provide a level of specificity that allows targeted intervention and minimises negative effects on non-target species. Sand flies mate using a leking strategy, where large numbers of males and females accumulate on trees or patches on the ground. The pheromone will initiate and stabilise these assemblies for targeted insecticide treatment or netting. This approach has been investigated in mosquito control, and would be expected to be more effective with Lutzomyia due to their behaviour of leking close to the ground, rather than in airborne swarms The sex and aggregation pheromone of Lutzomyia longipalpis is produced by the male and is attractive to both females and males of the species. Composition of the pheromone varies with geographical location, which results in a small number of 'chemotypes' of the insect. In Brazil, populations producing (S)-9-methylgermacrene-B ((S)-9MGB), (1S,3S,7R)-3-methyl-alpha-himachalene ((1S,3S,7R)-3MAH), or sobralene as the pheromone have been identified. Total chemical synthesis of these compounds is uneconomic, but by elucidating the biosynthesis and identifying the enzymes responsible for their synthesis in the insect, sustainable biocatalytic production can be realised. The potential future impact of this work in facilitating vector control, and thereby reducing cases of leishmaniasis, is therefore significant. In this project, which comes under BBSRC's Bioscience for Health research heading, a series of six work packages will be used to elucidate the biosynthesis of the three pheromone compounds. We will exploit the existence of the different chemotypes for comparative transcriptome and proteome analysis, which - supported with existing genomic data - will point to the biosynthetic enzymes in each population. This parallel approach using transcriptomics, proteomics and genomic data will maximise the probability of identifying the pheromone biosynthetic machinery. Once identified, the enzymes will be expressed for functional characterisation and for sustainable production of the pheromone for mass trapping, and ultimately disease control.