Predicted iron metabolism genes in hard ticks and their response to iron reduction in Dermacentor andersoni cells

Authors: SOLYMAN, MUNA - Washington State University; BRAYTON, KELLY - Washington State University; SHAW, DANA - Washington State University; OMSLAND, ANDERS - Washington State University; MCGEEHAN, STEVEN - University Of Idaho; Scoles, Glen; Noh, Susan

Submitted to: Ticks and Tick Borne Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/17/2020
Publication Date: 10/5/2020
Citation: Solyman, M., Brayton, K.A., Shaw, D.K., Omsland, A., McGeehan, S., Scoles, G.A., Noh, S.M. 2020. Predicted iron metabolism genes in hard ticks and their response to iron reduction in Dermacentor andersoni cells. Ticks and Tick Borne Diseases. 12(1). Article 101584. https://doi.org/10.1016/j.ttbdis.2020.101584.
DOI: https://doi.org/10.1016/j.ttbdis.2020.101584

Interpretive Summary: Ticks and tick-borne pathogens cause a significant disease burden in humans and animals and few vaccines are available to prevent these diseases. Consequently, tick control is the foundation of disease prevention. The available tick control methods are inadequate, in large part due to an overall lack of understanding of tick physiology. Ticks rely solely on blood as a source of nutrition, which presents some physiologic challenges for the tick and opportunities for the development of improved tick control methods. One physiologic challenge is maintaining iron homeostasis due to the potentially high iron load in the blood meal. Iron is essential for many cellular processes and all aspects of iron metabolism are tightly regulated in nearly all organisms. Genes and their products involved in iron metabolism, and the specific roles they play are poorly understood in ticks. We identified and sequenced 13 genes likely to be involved in iron metabolism in ticks. We then developed a method to reduce iron in cultured tick cells and measured the transcriptional response of each gene to iron reduction. Overall, the tick cells were relatively tolerant to iron depletion and nearly all genes were down-regulated in response to reduced iron. This is not surprising as ticks spend over 95% of their lives off of the host and thus must withstand long periods of fasting. The successful depletion of tick cells of iron will serve as useful tool for understanding iron metabolism in ticks and identifying targets for the development of novel anti-tick products.

Technical Abstract: For most organisms, iron is an essential nutrient due to its role in fundamental cellular processes. Insufficient iron causes sub-optimal metabolism with potential effects on viability, while high levels of iron are toxic due to the formation of oxidative radicals, which damage cellular components. As obligate hematophagous parasites, ticks are exposed to large amounts of iron in the blood meal. Many molecules and processes employed in iron uptake, storage, transport and metabolism are conserved, however significant knowledge gaps remain regarding these processes in ticks due to their unique physiology. In this study, we first identified and sequenced 13 genes likely to be involved in iron metabolism in Dermacentor andersoni tick cells. We then developed a method to reduce iron levels in D. andersoni tick cells using the iron chelator 2,2'-bipyridyl and measured the transcriptional response of these genes to iron reduction. The genes include a putative transferrin receptor, divalent metal transporter 1, duodenal cytochrome b, zinc/iron transporters zip7, zip13, zip14, mitoferrin, ferrochelatase, iron regulatory protein 1, ferritin1, ferritin2, transferrin and poly r(C)-binding protein. Overall, the transcriptional response of the target genes to iron reduction was modest. The most marked changes were a decrease in ferritin2, which transports iron through the tick hemolymph, the mitochondrial iron transporter mitoferrin, and the mitochondrial enzyme ferrochelatase. Iron regulatory protein1 was the only gene with an overall increase in transcript in response to reduced iron levels. This work lays the foundation for an improved understanding of iron metabolism in ticks which may provide molecular targets for the development of novel tick control methods and aid in the understanding of tick-pathogen interactions.