In the current fiscal year we have advanced our knowledge on novel proteins in saliva of blood feeding ticks and mosquitoes. Specifically, we discovered a novel protein found in saliva of mosquitoes that prevents collagen from triggering platelet adhesion and aggregation by different receptor interactions (1), characterized a second cystatin from the tick vector of Lyme disease with pharmacological potential (2) and identified prostaglandin E2 as the major salivary constituent of Ixodes scapularis (the main vector of Lyme disease in the US) that prevents antigen presentation by dendritic cells, and thus is a major immunosuppressive agent in tick saliva. ? ? We have also increased our salivary transcriptomes database by exploring the salivary transcriptome of vector species so far undescribed, such as the vector of human plague, the flea Xenopsylla cheopis (4), the mosquitoes Aedes albopictus (5) and Anopheles funestus (6), and the vector of Chagas disease, Triatoma brasiliensis (7). We have also expanded the EST coverage of the salivary transcriptome of Aedes aegypti (8), the main vector of Dengue in the World. To better understand the evolution of gene families associated with salivary function, we also sequenced and analyzed a salivary transcriptome of the seed feeding bug, Oncopeltus fasciatus (9), which is closely related to blood sucking bugs. Each transcriptome uncovers dozens of novel protein families which represent a rich resource for mining pharmacologically active and antimicrobial compounds.? ? Our bioinformatic capability allowed us to collaborate with other research groups inside and outside the NIAID, leading on this fiscal year to a publication with the group of Dr. X. Su (LMVR/NIAID) on gene predictions within the malaria parasite genome of Plasmodium falciparum (10), and with Dr. Nora Besansky's group at Notre Dame on the genome structure of Anopheles gambiae.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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Santiago, Paula Beatriz; de Araújo, Carla Nunes; Charneau, Sébastien et al. (2018) Exploring the molecular complexity of Triatoma dimidiata sialome. J Proteomics 174:47-60
Fernández-Medina, R D; Granzotto, A; Ribeiro, J M et al. (2016) Transposition burst of mariner-like elements in the sequenced genome of Rhodnius prolixus. Insect Biochem Mol Biol 69:14-24
Ribeiro, José M C; Schwarz, Alexandra; Francischetti, Ivo M B (2015) A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera). J Med Entomol 52:351-8
Ribeiro, José M C; Kazimirova, Maria; Takac, Peter et al. (2015) An insight into the sialome of the horse fly, Tabanus bromius. Insect Biochem Mol Biol 65:83-90
Francischetti, Ivo M B; Assumpção, Teresa C F; Ma, Dongying et al. (2013) The ""Vampirome"": Transcriptome and proteome analysis of the principal and accessory submaxillary glands of the vampire bat Desmodus rotundus, a vector of human rabies. J Proteomics 82:288-319
Ronca, Raffaele; Kotsyfakis, Michalis; Lombardo, Fabrizio et al. (2012) The Anopheles gambiae cE5, a tight- and fast-binding thrombin inhibitor with post-transcriptionally regulated salivary-restricted expression. Insect Biochem Mol Biol 42:610-20
Francischetti, Ivo M B; Oliveira, Carlo J; Ostera, Graciela R et al. (2012) Defibrotide interferes with several steps of the coagulation-inflammation cycle and exhibits therapeutic potential to treat severe malaria. Arterioscler Thromb Vasc Biol 32:786-98
Ribeiro, Jose M C; Mans, Ben J; Arca, Bruno (2010) An insight into the sialome of blood-feeding Nematocera. Insect Biochem Mol Biol :
Struchiner, Claudio J; Massad, Eduardo; Tu, Zhijian et al. (2009) The tempo and mode of evolution of transposable elements as revealed by molecular phylogenies reconstructed from mosquito genomes. Evolution 63:3136-46
Calvo, Eric; Pham, Van M; Marinotti, Osvaldo et al. (2009) The salivary gland transcriptome of the neotropical malaria vector Anopheles darlingi reveals accelerated evolution of genes relevant to hematophagy. BMC Genomics 10:57

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