Ticks, and other blood-feeding arthropod vectors, manipulate host homeostatic responses by secreting molecules from their multifunctional salivary glands. In their quest for a blood meal, ticks, and other blood-feeding arthropod vectors, transmit pathogens to their vertebrate hosts. Rickettsiosis is a great example of vector-borne diseases whose importance in public health is underappreciated. Understanding the interactions between vector and pathogen might help in developing strategies to combat arthropod-borne infections. Moreover, characterizing those tick proteins critical for feeding and transmission is essential to developing a molecular basis for new vaccines and therapeutics against tick-borne pathogens. Tick proteins that influence successful Spotted Fever Group Rickettsia (SFGR) infection represent potential candidates for vaccine and/or drug development. Our long-term goal is to reduce the spreading of vector- borne rickettsial disease by interfering with vector proteins. The overall objective of this R15 grant application is to elucidate the biological functin of newly identified selenoproteins in tick physiology and Spotted Fever Group Rickettsia (SFGR) transmission. In this application, we will test our central hypothesis that tick antioxidant factor (Selenoproteins) play an important physiological role by preventing oxidative stress during blood-feeding and protects invading rickettsial agents. This hypothesis will be tested by pursuing the following specific aims using a combination of biochemical, physiological, genetic and cell biological studies. 1) Investigate the physiological function of Amblyomma Selenoproteins in tick feeding success by preventing oxidative stress and inflammation, 2) Disrupt the oxidative balance in the tick to evaluate the tick feeding success and a novel Spotted Fever Group Rickettsia (SFGR) transmission to the host. The proposed work is innovative because the vector-borne pathogens are susceptible to oxidative stress;interference with redox metabolism represents a promising strategy for preventing tick-borne diseases. Results from this R15 research project are expected to demonstrate whether depletion of antioxidant factors in the tick saliva provide a new mechanism to eliminate the SFGR in tick vectors.
The proposed studies are important because they represent an approach to understanding significant tick vector/rickettsial interactions that contribute to rickettsial transmission potential with applicability to all Rickettsia/vector interactions. The proposed research is relevant to protecting public health because understanding spotted fever group rickettsia transmission could enhance research aimed at blocking Rickettsial transmission.
|Kumar, D; Budachetri, K; Meyers, V C et al. (2016) Assessment of tick antioxidant responses to exogenous oxidative stressors and insight into the role of catalase in the reproductive fitness of the Gulf Coast tick, Amblyomma maculatum. Insect Mol Biol 25:283-94|
|Budachetri, Khemraj; Gaillard, Daniel; Williams, Jaclyn et al. (2016) A snapshot of the microbiome of Amblyomma tuberculatum ticks infesting the gopher tortoise, an endangered species. Ticks Tick Borne Dis 7:1225-1229|
|Crispell, Gary; Budachetri, Khemraj; Karim, Shahid (2016) Rickettsia parkeri colonization in Amblyomma maculatum: the role of superoxide dismutases. Parasit Vectors 9:291|
|Budachetri, K; Karim, S (2015) An insight into the functional role of thioredoxin reductase, a selenoprotein, in maintaining normal native microbiota in the Gulf Coast tick (Amblyomma maculatum). Insect Mol Biol 24:570-81|
|Karim, Shahid; Ribeiro, JosÃ© M C (2015) An Insight into the Sialome of the Lone Star Tick, Amblyomma americanum, with a Glimpse on Its Time Dependent Gene Expression. PLoS One 10:e0131292|
|Budachetri, Khemraj; Browning, Rebecca E; Adamson, Steven W et al. (2014) An insight into the microbiome of the Amblyomma maculatum (Acari: Ixodidae). J Med Entomol 51:119-29|
|Huang, Kai-Fa; Hsu, Hui-Ling; Karim, Shahid et al. (2014) Structural and functional analyses of a glutaminyl cyclase from Ixodes scapularis reveal metal-independent catalysis and inhibitor binding. Acta Crystallogr D Biol Crystallogr 70:789-801|
|Adamson, S; Browning, R; Singh, P et al. (2014) Transcriptional activation of antioxidants may compensate for selenoprotein deficiencies in Amblyomma maculatum (Acari: Ixodidae) injected with selK- or selM-dsRNA. Insect Mol Biol 23:497-510|
|Mukherjee, Nabanita; Beati, Lorenza; Sellers, Michael et al. (2014) Importation of exotic ticks and tick-borne spotted fever group rickettsiae into the United States by migrating songbirds. Ticks Tick Borne Dis 5:127-34|
|Browning, R; Karim, S (2013) RNA interference-mediated depletion of N-ethylmaleimide sensitive fusion protein and synaptosomal associated protein of 25 kDa results in the inhibition of blood feeding of the Gulf Coast tick, Amblyomma maculatum. Insect Mol Biol 22:245-57|
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