Biotechnology and molecular biology of the alpha-glucosidase inhibitor acarbose. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. 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.Ĭhiasson, J. 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. Acarbose is an inhibitor of both human and bacterial α-glucosidases 3, limiting the ability of the target organism to metabolize complex carbohydrates. 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 1, 2, resulting in its inactivation. The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized.
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