Vector-Borne Diseases: Biology Of Vector Host Relationship

National Institute Of Allergy And Infectious Diseases

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Linked publications & trials

Abstract

Because host hemostasis (the physiological process that prevents blood loss, consisting of platelet aggregation, blood clotting and vasoconstriction) is a complex and redundant phenomenon, the salivary glands of blood sucking arthropods consist of a magic potion with diverse chemicals that in a redundant way counteract host mechanisms to prevent blood loss, allowing the fast acquisition of a meal. Salivary transcriptome made in the past few years indicate that the magic potion consists of 70-100 different proteins in the case of mosquitoes, for example, to over 1,000 in the case of ticks (Ticks feed for several days and have to disarm host immune reactions, in addition to the hemostatic system). Transcriptome studies also show that the salivary proteins of blood sucking arthropods are at a very fast pace of evolution, perhaps explaining why every genus studied so far has several unique protein families. Indeed, there are unique proteins found at the subgenus level. Given we can now describe in detail the sialotranscriptome (from the Greek word sialo = saliva) of a single organism, we can ask now what the universe of salivary proteins is associated to blood feeding, the so called sialoverse. There are near 19,000 species of blood sucking arthropods in 500 different genera. If we find (minimally) 5 novel protein families per genus (within the 70-500 proteins in each sialome), there are at least 2,500 novel proteins to be discovered, each one with an interesting pharmacological property. We have so far explored less than 20 genera of blood sucking arthropods, and it is our goal to extend sialotranscriptome discovery to map this pharmacological mine for future studies, and in the process learn the paths taken by genomes in their evolution to blood feeding and identify proteins with pharmacological and vaccine potential. While pursuing the theme above, Dr. Ribeiro has developed bioinformatic skills that were in high demand by laboratories within and outside NIAID, leading to many collaborative studies. During the 2020 fiscal year, members of the section of Vector Biology contributed to 10 publications, as described below: Transcriptomic studies In the current fiscal year, we produced 2 transcriptomic studies from the salivary glands of arthropod vectors, namely from the tick Amblyomma tuberculatum, the first such transcriptome of a tortoise-feeding tick (1), and from the sand fly Nyssomyia neivai, a vector of leishmaniasis in Brazil (2). We have also collaborated in transcriptomic studies of the digestive tract of flea vectors of plague (Xenopsylla cheopis) (3), the sensory organs of the mosquito Aedes albopictus (4), and towards the determination of protective antigens from the tick vector of Lyme disease, Ixodes ricinus (5). Functional studies Regarding functional studies of the salivary proteins of blood sucking arthropods, we characterized the structure and mechanism of action of salivary complement inhibitors of mosquitoes (6), a salivary peptide of the Yellow Fever Mosquito, Aedes aegypti, that modulates the function of macrophages (7), and we contributed to the structural characterization of a protein family expressed in the salivary glands of the West Nile vector Culex quinquefasciatus (8). Bioinformatic collaborations We participated in the gene annotation and salivary transcriptomic annotation of the stable fly, Stomoxys calcitrans (9), and we developed a new phylogenomics method based on a non-assisted tree construction based on the paired median ortholog amino-acid distance found in the deduced organism proteomes (10).