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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI093858-03
Application #
8513253
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero, Adriana
Project Start
2011-08-16
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$233,775
Indirect Cost
$69,275
Name
Texas A&M University
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
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
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 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
Lewis, Lauren A; Radulović, Željko M; Kim, Tae K et al. (2015) Identification of 24h Ixodes scapularis immunogenic tick saliva proteins. Ticks Tick Borne Dis 6:424-34
Porter, Lindsay; Radulović, 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
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
Ibelli, Adriana M G; Kim, Tae K; Hill, Creston C et al. (2014) A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting. Int J Parasitol 44:369-79
Radulović, Zeljko; Porter, Lindsay M; Kim, Tae K et al. (2014) Comparative bioinformatics, temporal and spatial expression analyses of Ixodes scapularis organic anion transporting polypeptides. Ticks Tick Borne Dis 5:287-98
Radulović, Željko M; Kim, Tae K; Porter, Lindsay M et al. (2014) A 24-48 h fed Amblyomma americanum tick saliva immuno-proteome. BMC Genomics 15:518
Kim, Tae K; Curran, Janet; Mulenga, Albert (2014) Dual silencing of long and short Amblyomma americanum acidic chitinase forms weakens the tick cement cone stability. J Exp Biol 217:3493-503

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