A catalytic carbohydrate contributes to bacterial antibiotic resistance.

Penicillins are widespread in nature and lethal to growing bacteria. Because of the severe threat posed by these antibiotics, bacteria have evolved a wide variety of strategies for combating them. Here, we describe one unusual strategy that involves the activity of a catalytic carbohydrate. We show that the cyclic oligosaccharide, beta-cyclodextrin (betaCD), can hydrolyze, and thereby inactivate, penicillin in vivo. Moreover, we demonstrate that this catalytic activity contributes to the antibiotic resistance of a bacterium that synthesizes this oligosaccharide in the laboratory. Taken together, these data not only expand our understanding of the biochemistry of penicillin resistance, but also provide the first demonstration of natural carbohydrate-mediated catalysis in a living system.