Dataset Information

Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion.

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.

SUBMITTER: Kotal J

PROVIDER: S-EPMC8161381 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion.

Kotál Jan J Buša Michal M Urbanová Veronika V Řezáčová Pavlína P Chmelař Jindřich J Langhansová Helena H Sojka Daniel D Mareš Michael M Kotsyfakis Michail M

International journal of molecular sciences 20210520 10

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 expressi ...[more]

PMID: 34065290

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Project description:BackgroundTicks are responsible for transmitting several notable pathogens worldwide. Finland lies in a zone where two human-biting tick species co-occur: Ixodes ricinus and Ixodes persulcatus. Tick densities have increased in boreal regions worldwide during past decades, and tick-borne pathogens have been identified as one of the major threats to public health in the face of climate change.MethodsWe used species distribution modelling techniques to predict the distributions of I. ricinus and I. persulcatus, using aggregated historical data from 2014 to 2020 and new tick occurrence data from 2021. By aiming to fill the gaps in tick occurrence data, we created a new sampling strategy across Finland. We also screened for tick-borne encephalitis virus (TBEV) and Borrelia from the newly collected ticks. Climate, land use and vegetation data, and population densities of the tick hosts were used in various combinations on four data sets to estimate tick species' distributions across mainland Finland with a 1-km resolution.ResultsIn the 2021 survey, 89 new locations were sampled of which 25 new presences and 63 absences were found for I. ricinus and one new presence and 88 absences for I. persulcatus. A total of 502 ticks were collected and analysed; no ticks were positive for TBEV, while 56 (47%) of the 120 pools, including adult, nymph, and larva pools, were positive for Borrelia (minimum infection rate 11.2%, respectively). Our prediction results demonstrate that two combined predictor data sets based on ensemble mean models yielded the highest predictive accuracy for both I. ricinus (AUC = 0.91, 0.94) and I. persulcatus (AUC = 0.93, 0.96). The suitable habitats for I. ricinus were determined by higher relative humidity, air temperature, precipitation sum, and middle-infrared reflectance levels and higher densities of white-tailed deer, European hare, and red fox. For I. persulcatus, locations with greater precipitation and air temperature and higher white-tailed deer, roe deer, and mountain hare densities were associated with higher occurrence probabilities. Suitable habitats for I. ricinus ranged from southern Finland up to Central Ostrobothnia and North Karelia, excluding areas in Ostrobothnia and Pirkanmaa. For I. persulcatus, suitable areas were located along the western coast from Ostrobothnia to southern Lapland, in North Karelia, North Savo, Kainuu, and areas in Pirkanmaa and Päijät-Häme.ConclusionsThis is the first study conducted in Finland that estimates potential tick species distributions using environmental and host data. Our results can be utilized in vector control strategies, as supporting material in recommendations issued by public health authorities, and as predictor data for modelling the risk for tick-borne diseases.

Project description:BackgroundReliable information on host use by arthropod vectors is required to study pathogen transmission ecology and to predict disease risk. Direct observation of host use is often difficult or impossible and indirect methods are therefore necessary. However, the reliability of currently available methods to identify the last host of blood-feeding arthropods has not been evaluated, and may be particularly problematic for ticks because host blood has been digested at capture. Biases in host detection may lead to erroneous conclusions on both vector ecology and pathogen circulation.MethodsHere, we experimentally tested for biases in host detection using the generalist three-host tick Ixodes ricinus as a model system. We fed ticks using an artificial feeding system and amplified blood meal traces post-moult (i.e., in the succeeding unfed life stage) via both a quantitative real-time polymerase chain reaction assay and a reverse line blotting method. We then experimentally tested for three types of biases in host detection: 1) time post-moult, 2) tick life stage and 3) host type (non-nucleated mammal blood versus nucleated avian blood), and compared these biases between the two molecular methods.ResultsOur results show that all three factors can influence host detection in ticks but not necessarily in the expected way. Although host detection rates decreased with time post-moult, mammal blood tended to be more readily detected than bird blood. Tick life stage was also an important factor; detection was higher in nymphs than in adults and, in some cases, remnants from both larval and nymphal blood meals could be detected in the adult stage. These biases were similar for the two detection techniques.ConclusionsWe show that different factors associated with questing ticks may influence our ability to correctly infer previous host use and that these factors may bias inferences from field-based studies. As these biases may be common to other vector-borne disease systems, their implications for our understanding of vector ecology and disease transmission require more explicit consideration.

Dataset Information

Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion.

Publications

Mialostatin, a Novel Midgut Cystatin from <i>Ixodes ricinus</i> Ticks: Crystal Structure and Regulation of Host Blood Digestion.

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