@article{4309,
  keywords = {Animals, Humans, Models, Molecular, Gastrointestinal Microbiome, Phosphotransferases (Alcohol Group Acceptor), Metagenome, Mouth, Drug Resistance, Bacterial, Inactivation, Metabolic, Hypoglycemic Agents, Acarbose, Amylases},
  author = {Jared Balaich and Michael Estrella and Guojun Wu and Philip Jeffrey and Abhishek Biswas and Liping Zhao and Alexei Korennykh and Mohamed Donia},
  title = {The human microbiome encodes resistance to the antidiabetic drug acarbose.},
  abstract = { <p>The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases, limiting the ability of the~target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.</p> },
  year = {2021},
  journal = {Nature},
  volume = {600},
  pages = {110-115},
  month = {2021 Dec},
  issn = {1476-4687},
  doi = {10.1038/s41586-021-04091-0},
  language = {eng},
}