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):

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