Title | The human microbiome encodes resistance to the antidiabetic drug acarbose. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Balaich, J, Estrella, M, Wu, G, Jeffrey, PD, Biswas, A, Zhao, L, Korennykh, A, Donia, MS |
Journal | Nature |
Volume | 600 |
Issue | 7887 |
Pagination | 110-115 |
Date Published | 2021 Dec |
ISSN | 1476-4687 |
Keywords | Acarbose, Amylases, Animals, Drug Resistance, Bacterial, Gastrointestinal Microbiome, Humans, Hypoglycemic Agents, Inactivation, Metabolic, Metagenome, Models, Molecular, Mouth, Phosphotransferases (Alcohol Group Acceptor) |
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> |
DOI | 10.1038/s41586-021-04091-0 |
Alternate Journal | Nature |
PubMed ID | 34819672 |
PubMed Central ID | 3552296 |
Grant List | R01 GM110161 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States 1013579 / WT_ / Wellcome Trust / United Kingdom DP2 AI124441 / AI / NIAID NIH HHS / United States P41 GM111244 / GM / NIGMS NIH HHS / United States |