N-acetyl ornithine deacetylase is a moonlighting protein and is involved in the adaptation of Entamoeba histolytica to nitrosative stress

Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite's survival in its host. In order to obtain insight into the mechanism of E. histolytica's adapt...

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Bibliographic Details
Published in:Scientific reports 2016-11, Vol.6 (1), p.36323, Article 36323
Main Authors: Shahi, Preeti, Trebicz-Geffen, Meirav, Nagaraja, Shruti, Hertz, Rivka, Alterzon-Baumel, Sharon, Methling, Karen, Lalk, Michael, Mazumder, Mohit, Samudrala, Gourinath, Ankri, Serge
Format: Article
Language:English
Subjects:
Adaptation
Amebiasis
Animals
Deacetylation
Dipeptides - metabolism
Entamoeba histolytica - enzymology
Entamoeba histolytica - genetics
Entamoeba histolytica - physiology
Gene expression
Gene Expression Profiling
Genes
Glyceraldehyde
Glyceraldehyde 3-phosphate
Glyceraldehyde-3-phosphate dehydrogenase
Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism
HeLa Cells
Humans
Mice
Nitric oxide
Nitrosative Stress
Ornithine
Ornithine Decarboxylase - genetics
Ornithine Decarboxylase - metabolism
Parasites
Phagocytes
Phosphate
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
RAW 264.7 Cells
Ribonucleic acid
RNA
S-Nitrosoglutathione - pharmacology
Sequence Analysis, RNA
Trophozoites
Up-Regulation
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Summary:Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite's survival in its host. In order to obtain insight into the mechanism of E. histolytica's adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is detrimental to E. histolytica exposed to NS and that this detrimental effect is neutralized by NAOD or by a catalytically inactive NAOD (mNAOD). These results establish NAOD as a moonlighting protein, and highlight the unexpected role of this metabolic enzyme in the adaptation of the parasite to NS.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep36323