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Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
Ixodes scapularis, the black-legged tick, vectors several human pathogens including Borrelia burgdorferi, the agent of Lyme disease in North America. Pathogen transmission to the vertebrate host occurs when infected ticks feed on the mammalian host to obtain a blood meal. Efforts to understand how t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706618/ https://www.ncbi.nlm.nih.gov/pubmed/23874485 http://dx.doi.org/10.1371/journal.pone.0068012 |
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author | Narasimhan, Sukanya Perez, Oriana Mootien, Sara DePonte, Kathleen Koski, Raymond A. Fikrig, Erol Ledizet, Michel |
author_facet | Narasimhan, Sukanya Perez, Oriana Mootien, Sara DePonte, Kathleen Koski, Raymond A. Fikrig, Erol Ledizet, Michel |
author_sort | Narasimhan, Sukanya |
collection | PubMed |
description | Ixodes scapularis, the black-legged tick, vectors several human pathogens including Borrelia burgdorferi, the agent of Lyme disease in North America. Pathogen transmission to the vertebrate host occurs when infected ticks feed on the mammalian host to obtain a blood meal. Efforts to understand how the tick confronts host hemostatic mechanisms and imbibes a fluid blood meal have largely focused on the anticoagulation strategies of tick saliva. The blood meal that enters the tick gut remains in a fluid state for several days during the process of feeding, and the role of the tick gut in maintaining the blood-meal fluid is not understood. We now demonstrate that the tick gut produces a potent inhibitor of thrombin, a key enzyme in the mammalian coagulation cascade. Chromatographic fractionation of engorged tick gut proteins identified one predominant thrombin inhibitory activity associated with an approximately 18 kDa protein, henceforth referred to as Ixophilin. The ixophilin gene was preferentially transcribed in the guts of feeding nymphs. Expression began after 24 hours of feeding, coincident with the flow of host blood into the tick gut. Immunity against Ixophilin delayed tick feeding, and decreased feeding efficiency significantly. Surprisingly, immunity against Ixophilin resulted in increased Borrelia burgdorferi transmission to the host, possibly due to delayed feeding and increased transmission opportunity. These observations illuminate the potential drawbacks of targeting individual tick proteins in a functional suite. They also underscore the need to identify the “anticoagulome” of the tick gut, and to prioritize a critical subset of anticoagulants that could be targeted to efficiently thwart tick feeding, and block pathogen transmission to the vertebrate host. |
format | Online Article Text |
id | pubmed-3706618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37066182013-07-19 Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis Narasimhan, Sukanya Perez, Oriana Mootien, Sara DePonte, Kathleen Koski, Raymond A. Fikrig, Erol Ledizet, Michel PLoS One Research Article Ixodes scapularis, the black-legged tick, vectors several human pathogens including Borrelia burgdorferi, the agent of Lyme disease in North America. Pathogen transmission to the vertebrate host occurs when infected ticks feed on the mammalian host to obtain a blood meal. Efforts to understand how the tick confronts host hemostatic mechanisms and imbibes a fluid blood meal have largely focused on the anticoagulation strategies of tick saliva. The blood meal that enters the tick gut remains in a fluid state for several days during the process of feeding, and the role of the tick gut in maintaining the blood-meal fluid is not understood. We now demonstrate that the tick gut produces a potent inhibitor of thrombin, a key enzyme in the mammalian coagulation cascade. Chromatographic fractionation of engorged tick gut proteins identified one predominant thrombin inhibitory activity associated with an approximately 18 kDa protein, henceforth referred to as Ixophilin. The ixophilin gene was preferentially transcribed in the guts of feeding nymphs. Expression began after 24 hours of feeding, coincident with the flow of host blood into the tick gut. Immunity against Ixophilin delayed tick feeding, and decreased feeding efficiency significantly. Surprisingly, immunity against Ixophilin resulted in increased Borrelia burgdorferi transmission to the host, possibly due to delayed feeding and increased transmission opportunity. These observations illuminate the potential drawbacks of targeting individual tick proteins in a functional suite. They also underscore the need to identify the “anticoagulome” of the tick gut, and to prioritize a critical subset of anticoagulants that could be targeted to efficiently thwart tick feeding, and block pathogen transmission to the vertebrate host. Public Library of Science 2013-07-09 /pmc/articles/PMC3706618/ /pubmed/23874485 http://dx.doi.org/10.1371/journal.pone.0068012 Text en © 2013 Narasimhan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Narasimhan, Sukanya Perez, Oriana Mootien, Sara DePonte, Kathleen Koski, Raymond A. Fikrig, Erol Ledizet, Michel Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis |
title | Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
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title_full | Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
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title_fullStr | Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
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title_full_unstemmed | Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
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title_short | Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
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title_sort | characterization of ixophilin, a thrombin inhibitor from the gut of ixodes scapularis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706618/ https://www.ncbi.nlm.nih.gov/pubmed/23874485 http://dx.doi.org/10.1371/journal.pone.0068012 |
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