RNAseq of C. elegans cultured on metformin sensitive and resistant E. coli strains with and without 50mM metformin treatment.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Caenorhabditis elegans
SUBMITTER: Rosina Pryor
PROVIDER: E-MTAB-7272 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Metformin is one of the most prescribed antidiabetic agents worldwide, and also considered for other therapeutic applications including cancer and endocrine disorders. Metformin is largely unmetabolised by human enzymes, and its mechanisms of action, likely also involving the microbiome, are not yet well characterised. Increasing presence of metformin in the environment has raised concerns, with reported toxic effects on aquatic life and potentially also on humans. We report on the isolation and characterisation of strain MD1, an aerobic methylotrophic bacterium growing with metformin as its sole carbon, nitrogen and energy source. Sequence analysis of its fully assembled genome allows its affiliation to Aminobacter niigataensis. Strain MD1 degrades metformin into dimethylamine used for growth, leaving guanylurea as a side-product. Differential proteomics and transcriptomics, as well as minitransposon mutagenesis of the strain, point to genes and proteins potentially associated with hydrolytic C-N cleavage of metformin, transport of metformin and guanylurea, and associated regulatory processes. Our results will inform future research on the fate of metformin and its degradation products in the human gut and the environment, and to identify microbial players and enzymes involved in the transformation of pharmaceuticals.
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