Attachment of Chlamydia trachomatis L2 to host cells requires sulfation
Chlamydia trachomatis is a pathogen responsible for a prevalent sexually transmitted disease. It is also the most common cause of infectious blindness in the developing world. We performed a loss-of-function genetic screen in human haploid cells to identify host factors important in C. trachomatis L...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2013
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| Online Access: | http://hdl.handle.net/1721.1/76744 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826205613554663424 |
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| author | Ploegh, Hidde Rosmarin, David M. Carette, Jan E. Olive, Andrew J. Starnbach, Michael N. Brummelkamp, Thijn R. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ploegh, Hidde Rosmarin, David M. Carette, Jan E. Olive, Andrew J. Starnbach, Michael N. Brummelkamp, Thijn R. |
| author_sort | Ploegh, Hidde |
| collection | MIT |
| description | Chlamydia trachomatis is a pathogen responsible for a prevalent sexually transmitted disease. It is also the most common cause of infectious blindness in the developing world. We performed a loss-of-function genetic screen in human haploid cells to identify host factors important in C. trachomatis L2 infection. We identified and confirmed B3GAT3, B4GALT7, and SLC35B2, which encode glucuronosyltransferase I, galactosyltransferase I, and the 3′-phosphoadenosine 5′-phosphosulfate transporter 1, respectively, as important in facilitating Chlamydia infection. Knockout of any of these three genes inhibits Chlamydia attachment. In complementation studies, we found that the introduction of functional copies of these three genes into the null clones restored full susceptibility to Chlamydia infection. The degree of attachment of Chlamydia strongly correlates with the level of sulfation of the host cell, not simply with the amount of heparan sulfate. Thus, other, as-yet unidentified sulfated macromolecules must contribute to infection. These results demonstrate the utility of screens in haploid cells to study interactions of human cells with bacteria. Furthermore, the human null clones generated can be used to investigate the role of heparan sulfate and sulfation in other settings not limited to infectious disease. |
| first_indexed | 2024-09-23T13:15:52Z |
| format | Article |
| id | mit-1721.1/76744 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:15:52Z |
| publishDate | 2013 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/767442022-10-01T14:06:16Z Attachment of Chlamydia trachomatis L2 to host cells requires sulfation Ploegh, Hidde Rosmarin, David M. Carette, Jan E. Olive, Andrew J. Starnbach, Michael N. Brummelkamp, Thijn R. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ploegh, Hidde Chlamydia trachomatis is a pathogen responsible for a prevalent sexually transmitted disease. It is also the most common cause of infectious blindness in the developing world. We performed a loss-of-function genetic screen in human haploid cells to identify host factors important in C. trachomatis L2 infection. We identified and confirmed B3GAT3, B4GALT7, and SLC35B2, which encode glucuronosyltransferase I, galactosyltransferase I, and the 3′-phosphoadenosine 5′-phosphosulfate transporter 1, respectively, as important in facilitating Chlamydia infection. Knockout of any of these three genes inhibits Chlamydia attachment. In complementation studies, we found that the introduction of functional copies of these three genes into the null clones restored full susceptibility to Chlamydia infection. The degree of attachment of Chlamydia strongly correlates with the level of sulfation of the host cell, not simply with the amount of heparan sulfate. Thus, other, as-yet unidentified sulfated macromolecules must contribute to infection. These results demonstrate the utility of screens in haploid cells to study interactions of human cells with bacteria. Furthermore, the human null clones generated can be used to investigate the role of heparan sulfate and sulfation in other settings not limited to infectious disease. National Institutes of Health (U.S.) (Grant R01 AI 033456) National Institutes of Health (U.S.) (Grant R01 AI 087879) 2013-02-06T16:00:41Z 2013-02-06T16:00:41Z 2012-06 2011-12 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/76744 Rosmarin, D. M. et al. “Attachment of Chlamydia Trachomatis L2 to Host Cells Requires Sulfation.” Proceedings of the National Academy of Sciences 109.25 (2012): 10059–10064. © 2012 National Academy of Sciences https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1073/pnas.1120244109 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Ploegh, Hidde Rosmarin, David M. Carette, Jan E. Olive, Andrew J. Starnbach, Michael N. Brummelkamp, Thijn R. Attachment of Chlamydia trachomatis L2 to host cells requires sulfation |
| title | Attachment of Chlamydia trachomatis L2 to host cells requires sulfation |
| title_full | Attachment of Chlamydia trachomatis L2 to host cells requires sulfation |
| title_fullStr | Attachment of Chlamydia trachomatis L2 to host cells requires sulfation |
| title_full_unstemmed | Attachment of Chlamydia trachomatis L2 to host cells requires sulfation |
| title_short | Attachment of Chlamydia trachomatis L2 to host cells requires sulfation |
| title_sort | attachment of chlamydia trachomatis l2 to host cells requires sulfation |
| url | http://hdl.handle.net/1721.1/76744 https://orcid.org/0000-0002-1090-6071 |
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