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 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.
Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, P.O.B. 9649, 31096 Haifa Israel.
Preeti
P
Shahi
Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, P.O.B. 9649, 31096 Haifa Israel.
Meirav
M
Trebicz-Geffen
Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, P.O.B. 9649, 31096 Haifa Israel.
Shruti
S
Nagaraja
Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, P.O.B. 9649, 31096 Haifa Israel.
Rivka
R
Hertz
Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, P.O.B. 9649, 31096 Haifa Israel.
Sharon
S
Baumel-Alterzon
University of Greifswald, Institute of Biochemistry, Greifswald, Germany.
Karen
K
Methling
University of Greifswald, Institute of Biochemistry, Greifswald, Germany.
Michael
M
Lalk
Jawaharlal Nehru University School of Life Sciences, New Delhi, India.
Mohit
M
Mazumder
Jawaharlal Nehru University School of Life Sciences, New Delhi, India.
Gourinath
G
Samudrala
Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, P.O.B. 9649, 31096 Haifa Israel.
Serge
S
Ankri
D000818:Animals; D004151:Dipeptides / Q000378:metabolism; D004748:Entamoeba histolytica / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D000073039:Nitrosative Stress; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D000067996:RAW 264.7 Cells; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D017423:Sequence Analysis, RNA; D015854:Up-Regulation
D004151:Dipeptides; D015800:Protozoan Proteins; D026422:S-Nitrosoglutathione; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D009955:Ornithine Decarboxylase; C002939:ornithylaspartate