The molecular and cellular basis of olfactory response to tsetse fly attractants

Dipteran or true flies occupy nearly every terrestrial habitat, and have evolved to feed upon a wide variety of sources including fruit, pollen, decomposing animal matter, and even vertebrate blood. Here we analyze the molecular, genetic and cellular basis of odor response in the tsetse fly Glossina morsitans, which feeds on the blood of humans and their livestock, and is a vector of deadly trypanosomes. The G. morsitans antenna contains specialized subtypes of sensilla, some of which line a sensory pit not found in the fruit fly Drosophila. We characterize distinct patterns of G. morsitans Odor receptor (GmmOr) gene expression in the antenna. We devise a new version of the empty neuron heterologous expression system, and use it to functionally express several GmmOrs in a mutant olfactory receptor neuron (ORN) of Drosophila. GmmOr35 responds to 1-hexen-3-ol, an odorant found in human emanations, and also alpha-pinene, a compound produced by malarial parasites. Another receptor, GmmOr9, which is expressed in the sensory pit, responds to acetone, 2-butanone and 2-propanol. We confirm by electrophysiological recording that neurons of the sensory pit respond to these odorants. Acetone and 2-butanone are strong attractants long used in the field to trap tsetse. We find that 2-propanol is also an attractant for both G. morsitans and the related species G. fuscipes, a major vector of African sleeping sickness. The results identify 2-propanol as a candidate for an environmentally friendly and practical tsetse attractant. Taken together, this work characterizes the olfactory system of a highly distinct kind of fly, and it provides an approach to identifying new agents for controlling the fly and the devastating diseases that it carries. Author summary African trypanosomiasis, also known as sleeping sickness in humans and wasting disease in livestock, is a lethal and economically burdensome disease that afflicts rural communities throughout sub-Saharan Africa. The parasite that causes the disease is spread by the tsetse fly, which feeds on the blood of humans and their livestock. One effective strategy to control tsetse and the diseases that it carries has been to attract the fly into traps, or repel the fly, with odorants. The efficiency of this approach can be greatly improved through understanding of the molecular and cellular machinery of tsetse olfaction, and by identification of odorants that manipulate it. Here we provide findings on the anatomical, cellular, and molecular underpinnings of tsetse olfaction, which previously has been greatly understudied. We characterize the expression of odor receptors in the antenna and study their function with a new version of an in vivo expression system. We identify receptors that respond to ecologically relevant odors in the tsetse fly's environment. One receptor, which is expressed in an unusual pit structure, responds to odorants that attract tsetse and may mediate attraction. We identify an odorant that activates this receptor and that could be useful in combatting African trypanosomiasis.