Vector-Borne Diseases: Biology Of Vector Host Relationship

National Institute Of Allergy And Infectious Diseases

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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, including the annotation of arthropod vector genomes. During the 2025 fiscal year, members of the section of Vector Biology contributed to 5 publications, as described below: Transcriptomic studies: In the current fiscal year, we produced the salivary transcriptomic studies of the house fly, Musca domestica (1) and the body louse Pediculus humanus (2). Genomic studies: We have disclosed the genome of the rat flea vector of human plague Xenopsylla cheopis, together with its Wolbachia endosymbiont (3). Functional studies: We have solved the structure and mode of action of a mosquito salivary anticomplement protein (4). Bioinformatic collaborations: In collaboration with Dr. Lucas Tirloni from RML we collaborated with the temporal annotation of tick midgut transcriptomes in their diverse phases of blood feeding (5). Future Plans: We will continue to address studies regarding the sialome switch of the tick vector of Lyme disease, Ixodes scapularis. We also plan the functional studies of metalloproteoid proteins, the recently discovered novel family of tick salivary proteins. Bibliography: 1) Stephen Lu, Noa Miller, Adrian Wilson, Christopher J. Geden, John G. Stoffolano and Jose M. C. Ribeiro (2025). A deep insight into the sialome of the house fly, Musca domestica, infected with the salivary gland hypertrophy virus (MdSGHV). Sci Rep 15, 8047. 2) Bland, D.M., Lu, S., Mahmood, S. and Ribeiro, J.M. (2025). An insight into the salivary gland content of the human body louse, Pediculus humanus. Sci Rep 15, 18322. https://doi.org/10.1038/s41598-025-01412-5 3) Stephen Lu, David M Bland, Eric Dahlstrom, Neelam Redekar, Melina G Guizzo, Kent Barbian, B Joseph Hinnebusch and José MC Ribeiro. (2025)An insight into the draft genome of the Oriental rat flea, Xenopsylla cheopis, together with its Wolbachia endosymbiont. BMC genomics 26 (1), 621 4) JF Andersen, H Lei, EC Strayer, V Pham, JMC Ribeiro. (2024) Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM. Communications Biology 7 (1), 649 5) S Lu, LC de Sousa-Paula, JMC Ribeiro, L Tirloni. (2024). Exploring the longitudinal expression dynamics of midguts in adult female Amblyomma americanum ticks. BMC genomics 25 (1), 996