The Phlebotomus papatasi transcriptomic response to trypanosomatid-contaminated blood is robust but non-specific

Abstract

The Phlebotomus papatasi transcriptomic response to trypanosomatid-contaminated 1 blood is robust but non-specific 2 3 4 5 6 Abstract 24 Leishmaniasis, caused by parasites of the genus Leishmania, is a disease that effects up to 8 25 million people worldwide. Parasites are transmitted to human and animal hosts through the 26 bite of an infected sand fly. Novel strategies for disease control, require a better 27 understanding of the key step for transmission namely, the establishment of infection inside 28 the fly. In this work we wanted to identify fly transcriptomic signatures associated with 29 infection success or failure. We used next generation sequencing to describe the 30 transcriptome of the sand fly Phlebotomus papatasi when fed with blood alone or with blood 31 containing one of three trypanosomatids: Leishmania major, Leishmania donovani and 32Herpetomonas muscarum: a parasite not transmitted to humans. Of these, only L. major was 33 able to successfully establish an infection in P. papatasi. However, the transcriptional 34 signatures observed were not specific to success or failure of infection but a generalised 35 response to the blood meal. This implies that sand flies perceive Leishmania as just a feature 36 of their microbiome landscape and that any strategy to tackle transmission should focus on 37 the response towards the blood meal rather than parasite establishment. 38 39 40 3 Authors summary 41 Leishmania are parasites that cause leishmaniasis, a group of serious diseases that affect 42 millions of people, mainly across the subtropics and tropics. They are transmitted to humans 43 by phlebotomine sand flies. However, despite establishment in the insect's midgut being key 44 to transmission, early infection events inside the insect are still unclear. Here, we study the 45 gene expression response of the insect vector to a Leishmania parasite that is able to establish 46 infection (L. major) one that is unable to do so (L. donovani) as well as one that is not a natural 47 parasite of sand flies (Herpetomonas muscarum). We found that responses following any of 48 the infected blood meals was very similar to uninfected blood meal. However, changes post-49 blood meal from day 1 to day 9 were dramatic. As a blood feeding insect can accumulate 50 three times its weight in one blood meal, this seems to be the most important physiological 51 change rather than the presence of the parasite. The latter might be just one in a number of 52 microbes the insect encounters. This result will generate new thinking around the concept of 53 stopping transmission by controlling the parasite inside the insect. 54 55