An NAD+-dependent novel transcription factor controls stage conversion in Entamoeba
Developmental switching between life-cycle stages is a common feature among parasitic pathogens to facilitate disease transmission and pathogenesis. The protozoan parasite Entamoeba switches between invasive trophozoites and dormant cysts, but the encystation process remains poorly understood despit...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/37912 |
| _version_ | 1828107627910922240 |
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| author | Dipak Manna Christian Stephan Lentz Gretchen Marie Ehrenkaufer Susmitha Suresh Amrita Bhat Upinder Singh |
| author_facet | Dipak Manna Christian Stephan Lentz Gretchen Marie Ehrenkaufer Susmitha Suresh Amrita Bhat Upinder Singh |
| author_sort | Dipak Manna |
| collection | DOAJ |
| description | Developmental switching between life-cycle stages is a common feature among parasitic pathogens to facilitate disease transmission and pathogenesis. The protozoan parasite Entamoeba switches between invasive trophozoites and dormant cysts, but the encystation process remains poorly understood despite being central to amoebic biology. We identify a transcription factor, Encystation Regulatory Motif-Binding Protein (ERM-BP), that regulates encystation. Down-regulation of ERM-BP decreases encystation efficiency resulting in abnormal cysts with defective cyst walls. We demonstrate that direct binding of NAD+ to ERM-BP affects ERM-BP conformation and facilitates its binding to promoter DNA. Additionally, cellular NAD+ levels increase during encystation and exogenous NAD+ enhances encystation consistent with the role of carbon source depletion in triggering Entamoeba encystation. Furthermore, ERM-BP catalyzes conversion of nicotinamide to nicotinic acid, which might have second messenger effects on stage conversion. Our findings link the metabolic cofactors nicotinamide and NAD+ to transcriptional regulation via ERM-BP and provide the first mechanistic insights into Entamoeba encystation. |
| first_indexed | 2024-04-11T10:35:13Z |
| format | Article |
| id | doaj.art-f18984e3b8e1407a8dcc9d32d26c4276 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:35:13Z |
| publishDate | 2018-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f18984e3b8e1407a8dcc9d32d26c42762022-12-22T04:29:20ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.37912An NAD+-dependent novel transcription factor controls stage conversion in EntamoebaDipak Manna0https://orcid.org/0000-0001-5112-3957Christian Stephan Lentz1Gretchen Marie Ehrenkaufer2Susmitha Suresh3Amrita Bhat4Upinder Singh5https://orcid.org/0000-0003-0630-0306Division of Infectious Diseases, Department of Internal Medicine, Stanford University School of Medicine, Stanford, United StatesDepartment of Pathology, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases, Department of Internal Medicine, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases, Department of Internal Medicine, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases, Department of Internal Medicine, Stanford University School of Medicine, Stanford, United StatesDivision of Infectious Diseases, Department of Internal Medicine, Stanford University School of Medicine, Stanford, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United StatesDevelopmental switching between life-cycle stages is a common feature among parasitic pathogens to facilitate disease transmission and pathogenesis. The protozoan parasite Entamoeba switches between invasive trophozoites and dormant cysts, but the encystation process remains poorly understood despite being central to amoebic biology. We identify a transcription factor, Encystation Regulatory Motif-Binding Protein (ERM-BP), that regulates encystation. Down-regulation of ERM-BP decreases encystation efficiency resulting in abnormal cysts with defective cyst walls. We demonstrate that direct binding of NAD+ to ERM-BP affects ERM-BP conformation and facilitates its binding to promoter DNA. Additionally, cellular NAD+ levels increase during encystation and exogenous NAD+ enhances encystation consistent with the role of carbon source depletion in triggering Entamoeba encystation. Furthermore, ERM-BP catalyzes conversion of nicotinamide to nicotinic acid, which might have second messenger effects on stage conversion. Our findings link the metabolic cofactors nicotinamide and NAD+ to transcriptional regulation via ERM-BP and provide the first mechanistic insights into Entamoeba encystation.https://elifesciences.org/articles/37912developmental controlEntamoeba histolyticatranscription factornicotinamideparasiteencystation |
| spellingShingle | Dipak Manna Christian Stephan Lentz Gretchen Marie Ehrenkaufer Susmitha Suresh Amrita Bhat Upinder Singh An NAD+-dependent novel transcription factor controls stage conversion in Entamoeba eLife developmental control Entamoeba histolytica transcription factor nicotinamide parasite encystation |
| title | An NAD+-dependent novel transcription factor controls stage conversion in Entamoeba |
| title_full | An NAD+-dependent novel transcription factor controls stage conversion in Entamoeba |
| title_fullStr | An NAD+-dependent novel transcription factor controls stage conversion in Entamoeba |
| title_full_unstemmed | An NAD+-dependent novel transcription factor controls stage conversion in Entamoeba |
| title_short | An NAD+-dependent novel transcription factor controls stage conversion in Entamoeba |
| title_sort | nad dependent novel transcription factor controls stage conversion in entamoeba |
| topic | developmental control Entamoeba histolytica transcription factor nicotinamide parasite encystation |
| url | https://elifesciences.org/articles/37912 |
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