The Use of Tick Salivary Proteins as Novel Therapeutics

Abstract

The last three decades of research into tick salivary components have revealed several proteins with important pharmacological and immunological activities. Two primary interests have driven research into tick salivary secretions: the search for suitable pathogen transmission blocking or "anti-tick" vaccine candidates and the search for novel therapeutics derived from tick salivary components. Intensive basic research in the field of tick salivary gland transcriptomics and proteomics has identified several major protein families that play important roles in tick feeding and overcoming vertebrate antitick responses. Moreover, these families contain members with unrealized therapeutic potential. Here we review the major tick salivary protein families exploitable in medical applications such as immunomodulation, inhibition of hemostasis and inflammation. Moreover, we discuss the potential, opportunities, and challenges in searching for novel tick-derived drugs.

Tick and Host Derived Compounds Detected in the Cement Complex Substance

“…Future studies using these data could be focused on the characterization of salivary gland proteins in early feeding stages of R. microplus. Finally, based on currently available information and the results obtained in this study, we predict that the characterization of the tick cementome will contribute to developing vaccines targeting tick adhesion and feeding for the control of tick infestations and pathogen transmission (Table S6) [14,20,[88][89][90] and new applications in medicine and industry as a biological glue [21,29,91]. Figure 9.…”

“…Ixodid ticks feed on blood for a relatively long period and an evolutionary adaptation to overcome host inflammatory and immune responses using molecules produced in tick salivary glands or recycled from the host and inoculated with saliva into the feeding site [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Cattle tick Rhipicephalus microplus (Canestrini, 1888) is an Ixodid one-host tick species (all developmental stages remain on the same host) with an impact on cattle industry in tropical and subtropical regions of the world [3,9,10].…”

Allergic Reactions and Immunity in Response to Tick Salivary Biogenic Substances and Red Meat Consumption in the Zebrafish Model

“…Tick saliva contains biogenic substances including proteins, lipids, and other biomolecules such as PGE 2 and α-Gal that modulate multiple biological processes affecting ectoparasite feeding and pathogen infection and transmission (Oliveira et al, 2011;Poole et al, 2013;Chmelar et al, 2019). These molecules may also affect host immune response leading to allergic diseases such as the AGS (Araujo et al, 2016;Cabezas-Cruz et al, 2017cChandrasekhar et al, 2019;Hilger et al, 2019).…”

“…Ticks are vectors of pathogens affecting human and animal health worldwide (de la Fuente et al, 2008(de la Fuente et al, , 2017. Tick saliva contains multiple biomolecules such as proteins and lipids that facilitate feeding while counteracting host defense responses, properties that also lead to possible application of these molecules in therapeutic interventions (Chmelar et al, 2019). However, tick bites themselves can induce a spectrum of inflammatory reactions in response to toxic and anticoagulant biogenic substances present in tick saliva and/or mouthpart penetration such as coagulative necrosis producing firm papules, tick paralysis, intense pruritus, tick bite alopecia, cutaneous lymphoid hyperplasia, and cell histiocytosis (Mihara, 2017;Stringer et al, 2017;Haddad et al, 2018;Ha et al, 2019).…”

Tick Salivary Compounds for Targeted Immunomodulatory Therapy

“…Tick salivary glands are now recognized as a rich source of pharmaco-active molecules (21). Tick saliva contains a rich cocktail of bioactive molecules including protein and lipid derivatives with a remarkable binding affinity, avidity, and selectivity for their targets in various host defense systems (22).…”