Blood anticlotting activity of a Rhipicephalus microplus cathepsin L-like enzyme

Xavier, Marina Amaral; Tirloni, Lucas; Torquato, Ricardo J.S.; Tanaka, Aparecida S.; Pinto, Antônio Frederico Michel; Diedrich, Jolene K.; Vaz, Itabajara da Silva; Seixas, Adriana; Termignoni, Carlos

doi:10.1016/j.biochi.2019.04.025

Cited by 13 publications

(11 citation statements)

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“…In a lone study, a cysteine protease from H. longicornis when silenced by RNAi, showed to be involved with digestion of a blood meal and increased the number of Babesia parasites (90). Recently, a cathepsin L from the tick, R. microplus (BmCL1), was shown to interact with thrombin at pH 7.5 and impair thrombin-induced fibrinogen clotting via a fibrinogenolytic activity (91). In helminths, cysteine proteases are the most abundant category of proteins identified into excretion/secretion products (92) and have been shown to be involved with host immune evasion (93) and extracellular matrix degradation (94).…”

Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

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24Amblyomma americanum ticks transmit more than a third of human tick-borne disease 25 (TBD) agents in the United States. Tick saliva proteins are critical to success of ticks as vectors 26 of TBD agents, and thus might serve as targets in tick antigen-based vaccines to prevent TBD 27 infections. We describe a systems biology approach to identify, by LC-MS/MS, saliva proteins 28 (tick=1182, rabbit=335) that A. americanum ticks likely inject into the host every 24 h during the 29 first 8 days of feeding, and towards the end of feeding using two different sample preparation 30 approaches (in-gel and in-solution). The in-gel approach determined molecular identification of 31 predominant protein bands in tick saliva, and the in-solution added depth to discovery of 32 proteins. Searching against entries in GenBank grouped tick and rabbit proteins in this study into 33 27 and 25 functional categories. Aside from housekeeping-like proteins, majority of tick saliva 34 proteins belong to the tick-specific (no homology to non-tick organisms: 32%), protease 35 inhibitors (13%), proteases (8%), glycine-rich proteins (6%) and lipocalins (4%) categories.36 Global secretion dynamics analysis suggests that majority (74%) of proteins in this study are 37 associated with regulating initial tick feeding functions and transmission of pathogens as they are 38 secreted within 24-48 h of tick attachment. Comparative analysis of the A. americanum tick 39 saliva proteome to five other tick saliva proteomes identified 284 conserved tick saliva proteins:40 we speculate that these regulate critical tick feeding functions and might serve as tick vaccine 41 antigens. We discuss our findings in the context of understanding A. americanum tick feeding 42 physiology as a means through which we can find effective targets for a vaccine against tick 43 feeding. 44 45 3 46 Author Summary 47The lone star tick, Amblyomma americanum, is a medically important species in US that 48 transmits 5 of the 16 reported tick-borne disease agents. Most recently, bites of this tick were 49 associated with red meat allergies in humans. Vaccination of animals against tick feeding has 50 been shown to be a sustainable and effective alternative to current acaricide based tick control 51 method which has several limitations. The pre-requisite to tick vaccine development is to 52 understand the molecular basis of tick feeding physiology. Toward this goal, this study has 53 identified proteins that A. americanum ticks inject into the host at different phases of its feeding 54 cycle. This data set has identified proteins that A. americanum inject into the host within 24-48 h 55 of feeding before it starts to transmit pathogens. Of high importance, we identified 284 proteins 56 that are present in saliva of other tick species, which we suspect regulate important role(s) in tick 57 feeding success and might represent rich source target antigens for a tick vaccine. Overall, this 58 study provides a foundation to understand the molecular mechanisms regulating tick feeding 59 p...

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Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

Self Cite

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“…Recently, a cathepsin L from the tick, R. microplus (BmCL1), was shown to interact with thrombin at pH 7.5 and impair thrombin-induced fibrinogen clotting via a fibrinogenolytic activity [95]. In helminths, cysteine proteases are the most abundant category of proteins identified into excretion/secretion products [96] and have been shown to be involved with host immune evasion [97] and extracellular matrix degradation [98].…”

Section: B) Majority Of Proteases In a Americanum Saliva Are Metallomentioning

confidence: 99%

Time-resolved proteomic profile of Amblyomma americanum tick saliva during feeding

et al. 2020

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Amblyomma americanum ticks transmit more than a third of human tick-borne disease (TBD) agents in the United States. Tick saliva proteins are critical to success of ticks as vectors of TBD agents, and thus might serve as targets in tick antigen-based vaccines to prevent TBD infections. We describe a systems biology approach to identify, by LC-MS/MS, saliva proteins (tick = 1182, rabbit = 335) that A. americanum ticks likely inject into the host every 24 h during the first 8 days of feeding, and towards the end of feeding. Searching against entries in GenBank grouped tick and rabbit proteins into 27 and 25 functional categories. Aside from housekeeping-like proteins, majority of tick saliva proteins belong to the tick-specific (no homology to non-tick organisms: 32%), protease inhibitors (13%), proteases (8%), glycine-rich proteins (6%) and lipocalins (4%) categories. Global secretion dynamics analysis suggests that majority (74%) of proteins in this study are associated with regulating initial tick feeding functions and transmission of pathogens as they are secreted within 24-48 h of tick attachment. Comparative analysis of the A. americanum tick saliva proteome to five other tick saliva proteomes identified 284 conserved tick saliva proteins: we speculate that these regulate critical tick feeding functions and might serve as tick vaccine antigens. We discuss our findings in the context of understanding A. americanum tick feeding physiology as a means through which we can find effective targets for a vaccine against tick feeding.

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“…Cysteine protease could be extracted from the leguminous Gliricidia sepium PBSGS using aqueous two-phase systems of sodium phosphate and PEG (da Silva et al, 2020); while serine proteases, which have the potential to degrade α, β and γ chains of fibrinogen and fibrin clots, could be extracted from different plants, including latex of Ficus carica, leaves of Cnidoscolus urens (L.), leaves of Petasites japonicas, latex of Artocarpus heterophyllus, leaves of Aster yomena, leaves of Allium tuberosum and latex of Euphorbia hirta (Chung et al, 2010a;Chung et al, 2010b;Patel et al, 2012;Siritapetawee et al, 2012;Choi et al, 2014;De Menezes et al, 2014;Kim et al, 2015;Hamed et al, 2020). Other sources of fibrinolytic enzymes include snake venoms, earthworms, sponge, and parasites (Cintra et al, 2012;Chou et al, 2013;Fu et al, 2013;Girón et al, 2013;Fu et al, 2016;Verma and Pulicherla, 2017;Dhamodharan et al, 2019;Xavier et al, 2019). Snake venoms contain metalloproteases, which are fibrinolytic enzymes consists of a group of multigene protein families involved in many activities of fibrinolysis, hemorrhage, apoptosis, anti-coagulant antiplatelet and pro-coagulant effects (Sanchez et al, 2017).…”

Section: Macro-organisms As Sources Of Fibrinolytic Enzymesmentioning

confidence: 99%

“…BmCL1 comprised of two isoforms with molecular weights of 26 and 22 kDa. It could degrade fibrinogen by hydrolyzing Aα-and Bβ-chains (Xavier et al, 2019).…”

Section: Macro-organisms As Sources Of Fibrinolytic Enzymesmentioning

confidence: 99%

Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy

Altaf

Kasim

2021

Front. Mol. Biosci.

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Thrombosis, a major cause of deaths in this modern era responsible for 31% of all global deaths reported by WHO in 2017, is due to the aggregation of fibrin in blood vessels which leads to myocardial infarction or other cardiovascular diseases (CVDs). Classical agents such as anti-platelet, anti-coagulant drugs or other enzymes used for thrombosis treatment at present could leads to unwanted side effects including bleeding complication, hemorrhage and allergy. Furthermore, their high cost is a burden for patients, especially for those from low and middle-income countries. Hence, there is an urgent need to develop novel and low-cost drugs for thrombosis treatment. Fibrinolytic enzymes, including plasmin like proteins such as proteases, nattokinase, and lumbrokinase, as well as plasminogen activators such as urokinase plasminogen activator, and tissue-type plasminogen activator, could eliminate thrombi with high efficacy rate and do not have significant drawbacks by directly degrading the fibrin. Furthermore, they could be produced with high-yield and in a cost-effective manner from microorganisms as well as other sources. Hence, they have been considered as potential compounds for thrombosis therapy. Herein, we will discuss about natural mechanism of fibrinolysis and thrombus formation, the production of fibrinolytic enzymes from different sources and their application as drugs for thrombosis therapy.

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Blood anticlotting activity of a Rhipicephalus microplus cathepsin L-like enzyme

Cited by 13 publications

References 39 publications

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Time-resolved proteomic profile of Amblyomma americanum tick saliva during feeding

Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy

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