Dramatic Increase in Glycerol Biosynthesis upon Oxidative Stress in the Anaerobic Protozoan Parasite Entamoeba histolytica

Afzal Husain, Dan Sato, Ghulam Jeelani, Tomoyoshi Soga, Tomoyoshi Nozaki

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Entamoeba histolytica, a microaerophilic enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. Trophozoites of E. histolytica are exposed to a variety of reactive oxygen and nitrogen species during infection. Since E. histolytica lacks key components of canonical eukaryotic anti-oxidative defense systems, such as catalase and glutathione system, alternative not-yet-identified anti-oxidative defense strategies have been postulated to be operating in E. histolytica. In the present study, we investigated global metabolic responses in E. histolytica in response to H2O2- and paraquat-mediated oxidative stress by measuring charged metabolites on capillary electrophoresis and time-of-flight mass spectrometry. We found that oxidative stress caused drastic modulation of metabolites involved in glycolysis, chitin biosynthesis, and nucleotide and amino acid metabolism. Oxidative stress resulted in the inhibition of glycolysis as a result of inactivation of several key enzymes, leading to the redirection of metabolic flux towards glycerol production, chitin biosynthesis, and the non-oxidative branch of the pentose phosphate pathway. As a result of the repression of glycolysis as evidenced by the accumulation of glycolytic intermediates upstream of pyruvate, and reduced ethanol production, the levels of nucleoside triphosphates were decreased. We also showed for the first time the presence of functional glycerol biosynthetic pathway in E. histolytica as demonstrated by the increased production of glycerol 3-phosphate and glycerol upon oxidative stress. We proposed the significance of the glycerol biosynthetic pathway as a metabolic anti-oxidative defense system in E. histolytica.

Original languageEnglish
Article numbere1831
JournalPLoS Neglected Tropical Diseases
Volume6
Issue number9
DOIs
Publication statusPublished - 2012 Sep

Fingerprint

Entamoeba histolytica
Glycerol
Parasites
Oxidative Stress
Glycolysis
Chitin
Biosynthetic Pathways
Amoebic Dysentery
Reactive Nitrogen Species
Pentose Phosphate Pathway
Trophozoites
Paraquat
Capillary Electrophoresis
Pyruvic Acid
Nucleosides
Catalase
Abscess
Glutathione
Reactive Oxygen Species
Mass Spectrometry

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Dramatic Increase in Glycerol Biosynthesis upon Oxidative Stress in the Anaerobic Protozoan Parasite Entamoeba histolytica. / Husain, Afzal; Sato, Dan; Jeelani, Ghulam; Soga, Tomoyoshi; Nozaki, Tomoyoshi.

In: PLoS Neglected Tropical Diseases, Vol. 6, No. 9, e1831, 09.2012.

Research output: Contribution to journalArticle

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