Sand flies are the exclusive vectors of the protozoan parasite Leishmania1, but the mechanism of transmission by fly bite has not been determined nor incorporated into experimental models of infection. In sand flies with mature Leishmania infections the anterior midgut is blocked by a gel of parasite origin, the promastigote secretory gel2,3. Here we analyse the inocula from Leishmania mexicana-infected Lutzomyia longipalpis sand flies. Analysis revealed the size of the infectious dose, the underlying mechanism of parasite delivery by regurgitation, and the novel contribution made to infection by filamentous proteophosphoglycan (fPPG), a component of promastigote secretory gel found to accompany the parasites during transmission. Collectively these results have important implications for understanding the relationship between the parasite and its vector, the pathology of cutaneous leishmaniasis in humans and also the development of effective vaccines and drugs. These findings emphasize that to fully understand transmission of vector-borne diseases the interaction between the parasite, its vector and the mammalian host must be considered together.
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The technical assistance of D. Moor and J. Archer is acknowledged. We thank M. Hajmova and P. Volf for assistance with the forced feeding technique and M. Wiese and P. Overath for antibodies and Leishmania mutants. This work received financial support from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Wellcome Trust, UK.
The authors declare that they have no competing financial interests.
Sand fly saliva is present but not adsorbed from egestion medium by DEAE-Sepharose. (PDF 114 kb)
Leishmania mexicana lipophosphoglycan (LPG) is not a component of PSG or found free in the sand fly gut. (PDF 88 kb)
Further evidence that the fPPG fraction of PSG is responsible for enhancement of Leishmania infectivity. (PDF 152 kb)
Culture-derived and sand fly egested Leishmania mexicana metacyclic promastigotes are of equal infectivity. (PDF 50 kb)
Sand fly salivary gland homogenate results in more disease exacerbation than saliva. (PDF 52 kb)
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Rogers, M., Ilg, T., Nikolaev, A. et al. Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature 430, 463–467 (2004). https://doi.org/10.1038/nature02675
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