Journal article

Transcriptomics Indicates Active and Passive Metronidazole Resistance Mechanisms in Three Seminal Giardia Lines

Brendan RE Ansell, Louise Baker, Samantha J Emery, Malcolm J McConville, Staffan G Svard, Robin B Gasser, Aaron R Jex

FRONTIERS IN MICROBIOLOGY | FRONTIERS MEDIA SA | Published : 2017

Abstract

Giardia duodenalis is an intestinal parasite that causes 200-300 million episodes of diarrhoea annually. Metronidazole (Mtz) is a front-line anti-giardial, but treatment failure is common and clinical resistance has been demonstrated. Mtz is thought to be activated within the parasite by oxidoreductase enzymes, and to kill by causing oxidative damage. In G. duodenalis, Mtz resistance involves active and passive mechanisms. Relatively low activity of iron-sulfur binding proteins, namely pyruvate:ferredoxin oxidoreductase (PFOR), ferredoxins, and nitroreductase-1, enable resistant cells to passively avoid Mtz activation. Additionally, low expression of oxygen-detoxification enzymes can allow p..

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Grants

Awarded by Australian Research Council (ARC)


Funding Acknowledgements

This work, including the efforts of AJ and MM, was funded by Australian Research Council (ARC) (LP120200122). BA, LB, SE, and AJ are supported by the Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme. BA is supported by an Australian Postgraduate Award (Australian Government) and the Victorian Life Sciences Computation Initiative (Victoria, Australia). RNA sequencing was partially funded by YourGene Biosciences (Taiwan). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.