Tiny ticks are vast sources of antihaemostatic factors

Abstract

Ticks are obligate blood-feeding ectoparasites. Damage of the skin of vertebrates leads to hemostatic, inflammatory and immune responses. These would disrupt tick feeding with detrimental consequences. To avoid host reactions, ticks inject saliva, a cocktail of pharmacologically active compounds, such as vasodilators, antiplatelet factors, anticoagulants, anti-inflammatory and immunomodulatory substances. Ticks have evolved powerful tools to prevent or prolong coagulation of the host blood. Majority of the inhibitors identified so far are proteins that display a variety of molecular masses, targets and inhibitory mechanisms. These anticoagulants can be classified as thrombin inhibitors, factor Xa inhibitors, extrinsic and intrinsic tenase complex inhibitors and contact system proteins inhibitors. Based on the diversity of antihemostatic strategies, it has been assumed that the main tick families have adapted to blood feeding independently. The key enzyme of the coagulation cascade - thrombin is often targeted by tick anticoagulants. The most well characterized thrombin inhibitors are the Kunitz-type proteinase inhibitors, i.e., ornithodorin, savignin and monobin from soft ticks, or boophilin, amblin, hemalin from hard ticks. A class of novel thrombin inhibitors is represented by variegin, isolated from the hard tick Amblyomma variegatum. This class of inhibitors display structural and functional similarity to hirulog, a peptide designed based on hirudin isolated from leech. TAP, a Kunitz-type FXa inhibitor from the soft tick Ornithodoros moubata has been among the best studied tick anticoagulants. Novel tick-derived molecules represent potentially useful therapeutic agents for treatment of hemostatic disorders, cardiovascular diseases and disorders of the immune system.