In the United States human vector borne diseases are primarily tick borne. The goals of this research are identification, characterization and validation of Amblyomma americanum and Ixodes scapularis tick saliva serine protease inhibitors (serpins) as vaccine target antigens for immunization of white tailed deer against tick infestation. To complete feeding, ticks must overcome host defense reactions, blood coagulation, complement activation and inflammation, all of which are serine protease mediated pathways that are tightly controlled by serpins. Our lab and others have proposed that during feeding, ticks express and inject serpins into the host to regulate evasion of host defense response to tick feeding activity. In an ongoing NIHR03 project in its final year we have screened 10 A. americanum (Aam) tick salivary gland (SG) serpin, and validated that 2 of the serpins (S), AamS6 and AamS8 are secreted into tick saliva, which is proxy for their injection into the host during tick feeding. We have extended these studies and identified 14 blood meal responsive I. scapularis tick SG serpins. In this proposal we will utilize protocols developed in the NIHR03 project to validate secretion of the 14 I. scapularis SG serpins into tick saliva. We have observed that the two A. americanum tick saliva serpins as well as the I. ricinus tick saliva serpin are highly conserved in ticks. Thus, we hypothesize that ticks utilize orthologous tick saliva serpins to regulate tick feeding and that immunologically blocking tick saliva serpin functions will prevent feeding success of multiple tick species. The importance of white tailed deer (Odocoileus virginianus) in the emergence of major human tick borne diseases (TBD) in the United States, Lyme disease, human anaplasmosis, babesiosis and ehrlichiosis and the southern tick-associated rash illness (STARI) has been recognized. Thus data in this proposal will be directly relevant towards efforts to develop novel technologies to prevent human TBD. There are 3 specific aims in this application. The first is to validate secretion of 16 blood meal responsive I. scapularis tick salivary gland serpins into tick saliva. The second is to characterize role(s) of A. americanum and I. scapularis native tick saliva serpins in tick feeding regulation. To validate tick immunity and anamnestic antibody response to tick infestation of white tailed deer immunized with recombinant tick saliva serpin antigens.
In the United States ticks transmit more vector borne disease agents than any other vector arthropod. Limitations associated with current acaricide based tick control strategies that threaten the future sustainability of containment programs for tick borne illnesses, have necessitated the need for development of alternative tick control strategies. Identification of important tick proteins that regulate tick physiology and facilitate tick feeding is important before alternative tick control methods can be developed.
|Radulovi?, Željko M; Mulenga, Albert (2017) Heparan sulfate/heparin glycosaminoglycan binding alters inhibitory profile and enhances anticoagulant function of conserved Amblyomma americanum tick saliva serpin 19. Insect Biochem Mol Biol 80:1-10|
|Porter, Lindsay M; Radulovi?, Željko M; Mulenga, Albert (2017) A repertoire of protease inhibitor families in Amblyomma americanum and other tick species: inter-species comparative analyses. Parasit Vectors 10:152|
|Tirloni, Lucas; Kim, Tae K; Pinto, Antônio F M et al. (2017) Tick-Host Range Adaptation: Changes in Protein Profiles in Unfed Adult Ixodes scapularis and Amblyomma americanum Saliva Stimulated to Feed on Different Hosts. Front Cell Infect Microbiol 7:517|
|Kim, Tae Kwon; Tirloni, Lucas; Pinto, Antônio F M et al. (2016) Ixodes scapularis Tick Saliva Proteins Sequentially Secreted Every 24 h during Blood Feeding. PLoS Negl Trop Dis 10:e0004323|
|Kim, Tae K; Radulovic, Zeljko; Mulenga, Albert (2016) Target validation of highly conserved Amblyomma americanum tick saliva serine protease inhibitor 19. Ticks Tick Borne Dis 7:405-14|
|Tirloni, Lucas; Kim, Tae Kwon; Coutinho, Mariana Loner et al. (2016) The putative role of Rhipicephalus microplus salivary serpins in the tick-host relationship. Insect Biochem Mol Biol 71:12-28|
|Kim, Tae Kwon; Tirloni, Lucas; Radulovic, Zeljko et al. (2015) Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions. Int J Parasitol 45:613-27|
|Lewis, Lauren A; Radulovi?, Željko M; Kim, Tae K et al. (2015) Identification of 24h Ixodes scapularis immunogenic tick saliva proteins. Ticks Tick Borne Dis 6:424-34|
|Radulovi?, Ž M; Porter, L M; Kim, T K et al. (2015) Amblyomma americanum tick saliva insulin-like growth factor binding protein-related protein 1 binds insulin but not insulin-like growth factors. Insect Mol Biol 24:539-50|
|Porter, Lindsay; Radulovi?, Željko; Kim, Tae et al. (2015) Bioinformatic analyses of male and female Amblyomma americanum tick expressed serine protease inhibitors (serpins). Ticks Tick Borne Dis 6:16-30|
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