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Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum.

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Title: Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum.
Authors: Vinayak, Sumiti, Pawlowic, Mattie C., Sateriale, Adam, Brooks, Carrie F., Studstill, Caleb J., Bar-Peled, Yael, Cipriano, Michael J., Striepen, Boris
Source: Nature. 7/23/2015, Vol. 523 Issue 7561, p477-480. 4p. 1 Color Photograph, 1 Diagram, 7 Graphs.
Subjects: Diarrhea, Cryptosporidium parvum, Genetic engineering, Parasites, Sporozoites, Palindromes
Abstract: Recent studies into the global causes of severe diarrhoea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrhoeal pathogen after rotavirus. Diarrhoeal disease is estimated to be responsible for 10.5% of overall child mortality. Cryptosporidium is also an opportunistic pathogen in the contexts of human immunodeficiency virus (HIV)-caused AIDS and organ transplantation. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger: malnourished children and immunocompromised patients. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes a lack of systems for continuous culture, facile animal models, and molecular genetic tools. Here we describe an experimental framework to genetically modify this important human pathogen. We established and optimized transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we developed a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, and in vivo selection for aminoglycoside resistance. We derived reporter parasites suitable for in vitro and in vivo drug screening, and we evaluated the basis of drug susceptibility by gene knockout. We anticipate that the ability to genetically engineer this parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection, and the role of parasite genes in these processes is now open to rigorous investigation. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum.
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  Data: <searchLink fieldCode="AR" term="%22Vinayak%2C+Sumiti%22">Vinayak, Sumiti</searchLink><br /><searchLink fieldCode="AR" term="%22Pawlowic%2C+Mattie+C%2E%22">Pawlowic, Mattie C.</searchLink><br /><searchLink fieldCode="AR" term="%22Sateriale%2C+Adam%22">Sateriale, Adam</searchLink><br /><searchLink fieldCode="AR" term="%22Brooks%2C+Carrie+F%2E%22">Brooks, Carrie F.</searchLink><br /><searchLink fieldCode="AR" term="%22Studstill%2C+Caleb+J%2E%22">Studstill, Caleb J.</searchLink><br /><searchLink fieldCode="AR" term="%22Bar-Peled%2C+Yael%22">Bar-Peled, Yael</searchLink><br /><searchLink fieldCode="AR" term="%22Cipriano%2C+Michael+J%2E%22">Cipriano, Michael J.</searchLink><br /><searchLink fieldCode="AR" term="%22Striepen%2C+Boris%22">Striepen, Boris</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 7/23/2015, Vol. 523 Issue 7561, p477-480. 4p. 1 Color Photograph, 1 Diagram, 7 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Diarrhea%22">Diarrhea</searchLink><br /><searchLink fieldCode="DE" term="%22Cryptosporidium+parvum%22">Cryptosporidium parvum</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+engineering%22">Genetic engineering</searchLink><br /><searchLink fieldCode="DE" term="%22Parasites%22">Parasites</searchLink><br /><searchLink fieldCode="DE" term="%22Sporozoites%22">Sporozoites</searchLink><br /><searchLink fieldCode="DE" term="%22Palindromes%22">Palindromes</searchLink>
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  Data: Recent studies into the global causes of severe diarrhoea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrhoeal pathogen after rotavirus. Diarrhoeal disease is estimated to be responsible for 10.5% of overall child mortality. Cryptosporidium is also an opportunistic pathogen in the contexts of human immunodeficiency virus (HIV)-caused AIDS and organ transplantation. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger: malnourished children and immunocompromised patients. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes a lack of systems for continuous culture, facile animal models, and molecular genetic tools. Here we describe an experimental framework to genetically modify this important human pathogen. We established and optimized transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we developed a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, and in vivo selection for aminoglycoside resistance. We derived reporter parasites suitable for in vitro and in vivo drug screening, and we evaluated the basis of drug susceptibility by gene knockout. We anticipate that the ability to genetically engineer this parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection, and the role of parasite genes in these processes is now open to rigorous investigation. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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