Supporting data for "Differential protein expression and post-translational modifications in Metronidazole-resistant Giardia duodenalis"

Dataset type: Proteomic
Data released on March 16, 2018

Emery SJ; Baker L; Ansell BRE; Mirzaei M; Haynes PA; McConville MJ; Svärd SG; Jex AR (2018): Supporting data for "Differential protein expression and post-translational modifications in Metronidazole-resistant Giardia duodenalis" GigaScience Database. http://dx.doi.org/10.5524/100416

DOI10.5524/100416

Metronidazole (Mtz) is the frontline drug treatment for multiple anaerobic pathogens, including the gastrointestinal protist, Giardia duodenalis. However, treatment failure is common and linked to in vivo drug resistance. In Giardia, in vitro drug-resistant lines allow controlled experimental interrogation of resistance mechanisms in isogenic cultures. However, resistance-associated changes are inconsistent between lines, phenotypic data are incomplete, and resistance is rarely genetically fixed, highlighted by reversion to sensitivity after drug selection ceases, or via passage through the life cycle. Comprehensive quantitative approaches are required to resolve isolate variability, fully define Mtz resistance phenotypes, and explore the role of post-translational modifications (PTMs) therein. We performed quantitative proteomics to describe differentially expressed proteins (DEPs) in three seminal Mtz resistant (MtzR) lines compared to their isogenic, Mtz-susceptible, parental line. We also probed changes in PTMs including protein acetylation, methylation, ubiquitination and phosphorylation via immunoblotting. We quantified over 1000 proteins in each genotype, recording substantial genotypic variation in DEPs between isotypes. Our data confirms substantial changes in the antioxidant network, glycolysis and electron transport, and indicates links between protein acetylation and Mtz resistance, including cross-resistance to deacetylase inhibitor Trichostatin A (TSA) in Mtz resistant lines. Finally, we performed the first controlled, longitudinal study of Mtz resistance stability, monitoring lines after cessation of drug selection, revealing isolate-dependent phenotypic plasticity. Our data demonstrate understanding of Mtz resistance must be broadened to post-transcriptional and post-translational responses, and that Mtz resistance is polygenic, driven by isolate-dependent variation, and is correlated with changes in protein acetylation networks.

Additional details

Read the peer-reviewed publication(s):

Emery, S. J., Baker, L., Ansell, B. R. E., Mirzaei, M., Haynes, P. A., McConville, M. J., … Jex, A. R. (2018). Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis. GigaScience, 7(4). doi:10.1093/gigascience/giy024

Accessions (data referenced by this study):

PRIDE: PXD007183





Sample IDTaxonomic IDCommon NameGenbank NameScientific NameSample Attributes
106_MtzR5741  Giardia intestinalis Description:Proteomics of Metronidazole Resistance...
Experiment type:Shotgun proteomics
PX-Modification:iodoacetamide derivatized residue,...
...
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106_MtzS5741  Giardia intestinalis Description:Proteomics of Metronidazole Resistance...
Experiment type:Shotgun proteomics
PX-Modification:iodoacetamide derivatized residue,...
...
+
713_MtzR5741  Giardia intestinalis Description:Proteomics of Metronidazole Resistance...
Experiment type:Shotgun proteomics
PX-Modification:iodoacetamide derivatized residue,...
...
+
713_MtzS5741  Giardia intestinalis Description:Proteomics of Metronidazole Resistance...
Experiment type:Shotgun proteomics
PX-Modification:iodoacetamide derivatized residue,...
...
+
WB_MtzR5741  Giardia intestinalis Description:Proteomics of Metronidazole Resistance...
Experiment type:Shotgun proteomics
PX-Modification:iodoacetamide derivatized residue,...
...
+
WB_MtzS5741  Giardia intestinalis Description:Proteomics of Metronidazole Resistance...
Experiment type:Shotgun proteomics
PX-Modification:iodoacetamide derivatized residue,...
...
+
Displaying 1-6 of 6 Sample(s).




File NameSample IDData TypeFile FormatSizeRelease Date 
ImageTIF28.56 MB2018-03-14
imageTIF6.59 MB2018-03-14
imageTIF7.17 MB2018-03-14
imageTIF4.45 MB2018-03-14
imageTIF28.56 MB2018-03-14
imageTIF6.8 MB2018-03-14
imageTIF7.19 MB2018-03-14
imageTIF4.59 MB2018-03-14
imageTIF7.19 MB2018-03-14
imageTIF7.75 MB2018-03-14
Displaying 1-10 of 47 File(s).
Funding body Awardee Award ID Comments
Australian Research Council MJ McConville AR Jex LP120200122
National Health and Medical Research Council AR Jex APP1126395 NHMRC Career Development Fellowship
The Jack Brockhoff Foundation SJ Emery 4184 Jack Brockhoff Foundation Early Career Grant
Date Action
March 16, 2018 Dataset publish
March 16, 2018 Title updated from : Supporting data for 'Differential protein expression and post-translational modifications in Metronidazole-resistant Giardia duodenalis'
July 4, 2018 Manuscript Link added : 10.1093/gigascience/giy024