4.5 Article

Nitroreductase Activites in Giardia lamblia: ORF 17150 Encodes a Quinone Reductase with Nitroreductase Activity

Journal

PATHOGENS
Volume 10, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/pathogens10020129

Keywords

anaerobic metabolism; drug susceptibility; functional assays; mass spectrometry; protein chromatography

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Funding

  1. Swiss National Science Foundation [31003A_163230]
  2. Swiss National Science Foundation (SNF) [31003A_163230] Funding Source: Swiss National Science Foundation (SNF)

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A novel enzyme with nitroreductase activity, encoded by ORF 17150, was identified in Giardia lamblia, providing insights into the resistance mechanisms of the parasite.
The intestinal diplomonadid Giardia lamblia is a causative agent of persistent diarrhea. Current treatments are based on nitro drugs, especially metronidazole. Nitro compounds are activated by reduction, yielding toxic intermediates. The enzymatic systems responsible for this activation are not completely understood. By fractionating cell free crude extracts by size exclusion chromatography followed by mass spectrometry, enzymes with nitroreductase (NR) activities are identified. The protein encoded by ORF 17150 found in two pools with NR activities is overexpressed and characterized. In pools of fractions with main NR activities, previously-known NRs are identified, as well as a previously uncharacterized protein encoded by ORF 17150. Recombinant protein 17150 is a flavoprotein with NADPH-dependent quinone reductase and NR activities. Besides a set of previously identified NRs, we have identified a novel enzyme with NR activity.

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