Dataset Information

Proteomics of Metronidazole Resistance in three seminal lines of Giardia duodenalis

ABSTRACT: Metronidazole (Mtz) is the frontline chemotherapeutic for a variety of anaerobic pathogens, including the gastroenterinal parasitic protist, Giardia duodenalis. However, treatment failure and clinical resistance is common and increasing. In Giardia, in vitro drug-resistant lines allow controlled experimental interrogation of resistance mechanisms in in vitro, isogenic cultures. These mechanisms centrally involve regulation of glycolytic and antioxidant oxidoreducatases, however this is inconsistent across isolate lines, likely incomplete, and further complicated by phenotypic plasticity in Giardia, which regains Mtz susceptibility after cessation of drug selection, or via passage through the life cycle. Global, quantitative approaches are required to reconstruct complex Mtz resistance phenotypes, resolve isolate variability, and explore unresolved hypotheses regarding post-translational modifications as the regulators of this phenotype. Our study addresses these gaps by comprehensively characterising proteomic changes in three seminal Mtz resistant lines compared to their isogenic, Mtz-susceptible, parental lines. Using quantitative proteomics, we have calculated differentially expressed proteins (DEPs) in MtzR lines, and probed via Western blot changes in protein acetylation, methylation, ubiquitination and phosphorylation post-translational modifications (PTMs). Finally, we have also performed the first controlled, longitudinal study

INSTRUMENT(S): Q Exactive

ORGANISM(S): Giardia Lamblia Atcc 50803

TISSUE(S): Trophozoite

DISEASE(S): Giardiasis

SUBMITTER: Samantha Emery

LAB HEAD: Aaron Jex

PROVIDER: PXD007183 | Pride | 2018-02-21

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	GiardiaMetTMT1.msf	Msf
	GiardiaMetTMT1T-TestRatios_proteingroups.txt	Txt
	GiardiaMetTMT3713.msf	Msf
	GiardiaMetTMT3713MtzRvsMtzSRatios_proteingroups.txt	Txt
	GiardiaMetTMT3T-TestratiosPooledRatio_proteingroups.txt	Txt

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Publications

Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis.

Emery Samantha J SJ Baker Louise L Ansell Brendan R E BRE Mirzaei Mehdi M Haynes Paul A PA McConville Malcom J MJ Svärd Staffan G SG Jex Aaron R AR

GigaScience 20180401 4

<h4>Background</h4>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 rarel ...[more]

PMID: 29688452

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