Abstract
The hard tick Ixodes ricinus is a vector of Lyme disease and tick-borne encephalitis. Host blood protein digestion, essential for tick development and reproduction, occurs in tick midgut digestive cells driven by cathepsin proteases. Little is known about the regulation of the digestive proteolytic machinery of I. ricinus. Here we characterize a novel cystatin-type protease inhibitor, mialostatin, from the I. ricinus midgut. Blood feeding rapidly induced mialostatin expression in the gut, which continued after tick detachment. Recombinant mialostatin inhibited a number of I. ricinus digestive cysteine cathepsins, with the greatest potency observed against cathepsin L isoforms, with which it co-localized in midgut digestive cells. The crystal structure of mialostatin was determined at 1.55 Å to explain its unique inhibitory specificity. Finally, mialostatin effectively blocked in vitro proteolysis of blood proteins by midgut cysteine cathepsins. Mialostatin is likely to be involved in the regulation of gut-associated proteolytic pathways, making midgut cystatins promising targets for tick control strategies.
Highlights
IntroductionTicks are globally distributed ectoparasitic arthropods that strictly feed on host blood.While soft ticks (family Argasidae) feed only for a few hours, hard ticks (family Ixodidae) usually attach to their hosts for several days to fully engorge and proceed to their developmental stage
Ticks are globally distributed ectoparasitic arthropods that strictly feed on host blood.While soft ticks feed only for a few hours, hard ticks usually attach to their hosts for several days to fully engorge and proceed to their developmental stage
As a result we found a highly similar transcript SigP-158801 upregulated mainly in the tick midgut [29]; to another transcript GCJO01026918.1 identified in a study focusing on the tick gut [30]
Summary
Ticks are globally distributed ectoparasitic arthropods that strictly feed on host blood.While soft ticks (family Argasidae) feed only for a few hours, hard ticks (family Ixodidae) usually attach to their hosts for several days to fully engorge and proceed to their developmental stage. Blood degrades in the acidic endolysosomes of digestive cells of the tick midgut. Albumin is directed to small acidic vesicles and hemoglobin to a population of large digestive vesicles [4]. Despite these differences, both albumin and hemoglobin are cleaved and processed to single amino acids and short peptides by the same proteolytic system [5,6]. Cysteine proteases with exopeptidase activity, cathepsins B and C (IrCB and IrCC), continue hemoglobin degradation to dipeptides at an optimal pH of 5.5–6.0 in digestive cells [6,10,11]. Blood processing by ticks and the roles of individual proteases are reviewed in detail elsewhere [12,13]
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