Kunitz domain-containing proteins are ubiquitous serine protease inhibitors with promising therapeutic potential. They target key proteases involved in major cellular processes such as inflammation or hemostasis through competitive inhibition in a substrate-like manner. Protease inhibitors from the Kunitz superfamily have a low molecular weight (18-24 kDa) and are characterized by the presence of one or more Kunitz motifs consisting of α-helices and antiparallel β-sheets stabilized by three disulfide bonds. Kunitz-type inhibitors are an important fraction of the protease inhibitors found in tick saliva. Their roles in inhibiting and/or suppressing host homeostatic responses continue to be shown to be additive or synergistic with other protease inhibitors such as cystatins or serpins, ultimately mediating successful blood feeding for the tick. In this review, we discuss the biochemical features of tick salivary Kunitz-type protease inhibitors. We focus on their various effects on host hemostasis and immunity at the molecular and cellular level and their potential therapeutic applications. In doing so, we highlight that their pharmacological properties can be exploited for the development of novel therapies and vaccines.

• Klíčová slova
• Kunitz-type, hemostasis, immunomodulation, parasite-host interactions, protease inhibitors, ticks,
• MeSH
• cystatiny * metabolismus   MeSH
• inhibitory serinových proteinas farmakologie   terapeutické užití   metabolismus   MeSH
• klíšťata * MeSH
• serpiny * metabolismus   MeSH
• sliny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cystatiny * MeSH
• inhibitory serinových proteinas MeSH
• serpiny * MeSH

BACKGROUND: The hard tick Hyalomma dromedarii is one of the most injurious ectoparasites affecting camels and apparently best adapted to deserts. As long-term blood feeders, ticks are threatened by host defense system compounds that can cause them to be rejected and, ultimately, to die. However, their saliva contains a cocktail of bioactive molecules that enables them to succeed in taking their blood meal. A recent sialotranscriptomic study uncovered the complexity of the salivary composition of the tick H. dromedarii and provided a database for a proteomic analysis. We carried out a proteomic-informed by transcriptomic (PIT) to identify proteins in salivary glands of both genders of this tick species. RESULTS: We reported the array of 1111 proteins identified in the salivary glands of H. dromedarii ticks. Only 24% of the proteins were shared by both genders, and concur with the previously described sialotranscriptome complexity. The comparative analysis of the salivary glands of both genders did not reveal any great differences in the number or class of proteins expressed their enzymatic composition or functional classification. Indeed, few proteins in the entire proteome matched those predicted from the transcriptome while others corresponded to other proteins of other tick species. CONCLUSION: This investigation represents the first proteomic study of H. dromedarii salivary glands. Our results shed light on the differences between the composition of H. dromedarii male and female salivary glands, thus enabling us to better understand the gender-specific strategy to feed successfully.

• Klíčová slova
• Hyalomma dromedarii, LC–MS/MS, PIT, Proteome, Salivary glands,
• MeSH
• klíšťata genetika   metabolismus   MeSH
• proteiny členovců genetika   metabolismus   MeSH
• proteom metabolismus   MeSH
• proteomika MeSH
• slinné žlázy metabolismus   MeSH
• sliny metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• velbloudi MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny členovců MeSH
• proteom MeSH

Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, a member of the "Basic-tail" family of salivary proteins from the tick Ixodes scapularis. Ixonnexin is a 104 residues (11.8 KDa), non-enzymatic basic protein which contains 3 disulfide bonds and a C-terminal rich in lysine. It is homologous to SALP14, a tick salivary FXa anticoagulant. Ixonnexin was produced by ligation of synthesized fragments (51-104) and (1-50) followed by folding. Ixonnexin, like SALP14, interacts with FXa. Notably, Ixonnexin also modulates fibrinolysis in vitro by a unique salivary mechanism. Accordingly, it accelerates plasminogen activation by tissue-type plasminogen activator (t-PA) with Km 100 nM; however, it does not affect urokinase-mediated fibrinolysis. Additionally, lysine analogue ε-aminocaproic acid inhibits Ixonnexin-mediated plasmin generation implying that lysine-binding sites of Kringle domain(s) of plasminogen or t-PA are involved in this process. Moreover, surface plasmon resonance experiments shows that Ixonnexin binds t-PA, and plasminogen (KD 10 nM), but not urokinase. These results imply that Ixonnexin promotes fibrinolysis by supporting the interaction of plasminogen with t-PA through formation of an enzymatically productive ternary complex. Finally, in vivo experiments demonstrates that Ixonnexin inhibits FeCl3-induced thrombosis in mice. Ixonnexin emerges as novel modulator of fibrinolysis which may also affect parasite-vector-host interactions.

• MeSH
• arteriální okluzní nemoci chemicky indukované   patologie   prevence a kontrola   MeSH
• chloridy toxicita   MeSH
• fibrinolýza účinky léků   MeSH
• klíšťata metabolismus   MeSH
• myši MeSH
• noxy toxicita   MeSH
• plazminogen metabolismus   MeSH
• slinné proteiny a peptidy farmakologie   MeSH
• sliny metabolismus   MeSH
• tkáňový aktivátor plazminogenu metabolismus   MeSH
• trombóza chemicky indukované   patologie   prevence a kontrola   MeSH
• železité sloučeniny toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• chloridy MeSH
• ferric chloride MeSH Prohlížeč
• noxy MeSH
• plazminogen MeSH
• slinné proteiny a peptidy MeSH
• tkáňový aktivátor plazminogenu MeSH
• železité sloučeniny MeSH

Adult females of the genus Ixodes imbibe blood meals exceeding about 100 times their own weight within 7‒9 days. During this period, ticks internalise components of host blood by endocytic digest cells that line the tick midgut epithelium. Using RNA-seq, we aimed to characterise the midgut transcriptome composition in adult Ixodes ricinus females during early and late phase of engorgement. To address specific adaptations to the haemoglobin-rich diet, we compared the midgut transcriptomes of genetically homogenous female siblings fed either bovine blood or haemoglobin-depleted serum. We noted that tick gut transcriptomes are subject to substantial temporal-dependent expression changes between day 3 and day 8 of feeding. In contrast, the number of transcripts significantly affected by the presence or absence of host red blood cells was low. Transcripts relevant to the processes associated with blood-meal digestion were analysed and involvement of selected encoded proteins in the tick midgut physiology discussed. A total of 7215 novel sequences from I. ricinus were deposited in public databases as an additional outcome of this study. Our results broaden the current knowledge of tick digestive system and may lead to the discovery of potential molecular targets for efficient tick control.

• MeSH
• klíště genetika   metabolismus   MeSH
• sekvenční analýza RNA * MeSH
• skot MeSH
• stanovení celkové genové exprese * MeSH
• střeva patologie   MeSH
• střevní sliznice metabolismus   MeSH
• transkriptom fyziologie   MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH