The publication of the first tick sialome (salivary gland transcriptome) heralded a new era of research of tick protease inhibitors, which represent important constituents of the proteins secreted via tick saliva into the host. Three major groups of protease inhibitors are secreted into saliva: Kunitz inhibitors, serpins, and cystatins. Kunitz inhibitors are anti-hemostatic agents and tens of proteins with one or more Kunitz domains are known to block host coagulation and/or platelet aggregation. Serpins and cystatins are also anti-hemostatic effectors, but intriguingly, from the translational perspective, also act as pluripotent modulators of the host immune system. Here we focus especially on this latter aspect of protease inhibition by ticks and describe the current knowledge and data on secreted salivary serpins and cystatins and their role in tick-host-pathogen interaction triad. We also discuss the potential therapeutic use of tick protease inhibitors.

• MeSH
• cystatiny fyziologie   terapeutické užití   MeSH
• imunomodulace MeSH
• inhibitory proteas klasifikace   metabolismus   terapeutické užití   MeSH
• inhibitory serinových proteinas fyziologie   terapeutické užití   MeSH
• interakce hostitele a parazita MeSH
• klíšťata metabolismus   MeSH
• lidé MeSH
• serpiny fyziologie   terapeutické užití   MeSH
• sliny enzymologie   metabolismus   MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The obligate intracellular pathogen, Anaplasma phagocytophilum, is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts. However, our current knowledge on how A. phagocytophilum affect these processes in the tick vector, Ixodes scapularis is limited. In this study, a genome-wide search for components of major carbohydrate metabolic pathways was performed in I. scapularis ticks for which the genome was recently published. The enzymes involved in the seven major carbohydrate metabolic pathways glycolysis, gluconeogenesis, pentose phosphate, tricarboxylic acid cycle (TCA), glyceroneogenesis, and mitochondrial oxidative phosphorylation and β-oxidation were identified. Then, the available transcriptomics and proteomics data was used to characterize the mRNA and protein levels of I. scapularis major carbohydrate metabolic pathway components in response to A. phagocytophilum infection of tick tissues and cultured cells. The results showed that major carbohydrate metabolic pathways are conserved in ticks. A. phagocytophilum infection inhibits gluconeogenesis and mitochondrial metabolism, but increases the expression of glycolytic genes. A model was proposed to explain how A. phagocytophilum could simultaneously control tick cell glucose metabolism and cytoskeleton organization, which may be achieved in part by up-regulating and stabilizing hypoxia inducible factor 1 alpha in a hypoxia-independent manner. The present work provides a more comprehensive view of the major carbohydrate metabolic pathways involved in the response to A. phagocytophilum infection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.

• MeSH
• Anaplasma phagocytophilum patogenita   fyziologie   MeSH
• anaplasmóza metabolismus   MeSH
• buněčné linie MeSH
• citrátový cyklus genetika   MeSH
• glukoneogeneze genetika   MeSH
• glykolýza genetika   MeSH
• interakce hostitele a patogenu genetika   MeSH
• klíště enzymologie   genetika   metabolismus   mikrobiologie   MeSH
• metabolické sítě a dráhy genetika   MeSH
• metabolismus sacharidů genetika   MeSH
• mitochondrie genetika   metabolismus   MeSH
• pentózofosfátový cyklus genetika   MeSH
• proteiny členovců chemie   genetika   metabolismus   MeSH
• proteomika metody   MeSH
• regulace genové exprese fyziologie   MeSH
• sacharidy MeSH
• slinné žlázy mikrobiologie   MeSH
• terciární struktura proteinů MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH