Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival.
NAD, a key co-enzyme required for cell metabolism, is synthesized via two pathways in most organisms. Since schistosomes apparently lack enzymes required for de novo NAD biosynthesis, we evaluated whether these parasites, which infect >200 million people worldwide, maintain NAD homeostasis via th...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008539 |
| _version_ | 1818589536769277952 |
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| author | Michael D Schultz Tulin Dadali Sylvain A Jacques Hélène Muller-Steffner Jeremy B Foote Leonardo Sorci Esther Kellenberger Davide Botta Frances E Lund |
| author_facet | Michael D Schultz Tulin Dadali Sylvain A Jacques Hélène Muller-Steffner Jeremy B Foote Leonardo Sorci Esther Kellenberger Davide Botta Frances E Lund |
| author_sort | Michael D Schultz |
| collection | DOAJ |
| description | NAD, a key co-enzyme required for cell metabolism, is synthesized via two pathways in most organisms. Since schistosomes apparently lack enzymes required for de novo NAD biosynthesis, we evaluated whether these parasites, which infect >200 million people worldwide, maintain NAD homeostasis via the NAD salvage biosynthetic pathway. We found that intracellular NAD levels decline in schistosomes treated with drugs that block production of nicotinamide or nicotinamide mononucleotide-known NAD precursors in the non-deamidating salvage pathway. Moreover, in vitro inhibition of the NAD salvage pathway in schistosomes impaired egg production, disrupted the outer membranes of both immature and mature parasites and caused loss of mobility and death. Inhibiting the NAD salvage pathway in schistosome-infected mice significantly decreased NAD levels in adult parasites, which correlated with reduced egg production, fewer liver granulomas and parasite death. Thus, schistosomes, unlike their mammalian hosts, appear limited to one metabolic pathway to maintain NAD-dependent metabolic processes. |
| first_indexed | 2024-12-16T09:42:13Z |
| format | Article |
| id | doaj.art-38618719737b47b3b9c46e6de53e10de |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T09:42:13Z |
| publishDate | 2020-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-38618719737b47b3b9c46e6de53e10de2022-12-21T22:36:15ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-05-01165e100853910.1371/journal.ppat.1008539Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival.Michael D SchultzTulin DadaliSylvain A JacquesHélène Muller-SteffnerJeremy B FooteLeonardo SorciEsther KellenbergerDavide BottaFrances E LundNAD, a key co-enzyme required for cell metabolism, is synthesized via two pathways in most organisms. Since schistosomes apparently lack enzymes required for de novo NAD biosynthesis, we evaluated whether these parasites, which infect >200 million people worldwide, maintain NAD homeostasis via the NAD salvage biosynthetic pathway. We found that intracellular NAD levels decline in schistosomes treated with drugs that block production of nicotinamide or nicotinamide mononucleotide-known NAD precursors in the non-deamidating salvage pathway. Moreover, in vitro inhibition of the NAD salvage pathway in schistosomes impaired egg production, disrupted the outer membranes of both immature and mature parasites and caused loss of mobility and death. Inhibiting the NAD salvage pathway in schistosome-infected mice significantly decreased NAD levels in adult parasites, which correlated with reduced egg production, fewer liver granulomas and parasite death. Thus, schistosomes, unlike their mammalian hosts, appear limited to one metabolic pathway to maintain NAD-dependent metabolic processes.https://doi.org/10.1371/journal.ppat.1008539 |
| spellingShingle | Michael D Schultz Tulin Dadali Sylvain A Jacques Hélène Muller-Steffner Jeremy B Foote Leonardo Sorci Esther Kellenberger Davide Botta Frances E Lund Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival. PLoS Pathogens |
| title | Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival. |
| title_full | Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival. |
| title_fullStr | Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival. |
| title_full_unstemmed | Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival. |
| title_short | Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival. |
| title_sort | inhibition of the nad salvage pathway in schistosomes impairs metabolism reproduction and parasite survival |
| url | https://doi.org/10.1371/journal.ppat.1008539 |
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