Abstract
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, β-cyclodextrin (βCD), 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.
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Acknowledgments
We thank Drs. Milton Gordon, Jim Staley, Marion Brodhagen, Robert Edmonds, and members of the Nester, Hakomori, and Gordon laboratories for their insightful comments and criticisms, and Drs. Carlos Semino and William J. Brown for stimulating discussions during the early stages of this work. Ms. Emily Lee and Mr. Adonis Acuario provided expert technical assistance. This work was supported by a National Science Foundation Small Grant for Exploratory Research (MCB-0135592) and a National Institutes of Health Research grant (GM 32618) to E. W. N., a National Institutes of Health/National Cancer Institute grant (R01-CA80054) to S. Hakomori that also provided support to T. H., and an American Cancer Society postdoctoral fellowship to P. dF.
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Communicated by K. Horikoshi.
Paul de Figueiredo, Becky Terra and Jasbir Kaur Anand have contributed equally to this work.
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de Figueiredo, P., Terra, B., Anand, J.K. et al. A catalytic carbohydrate contributes to bacterial antibiotic resistance. Extremophiles 11, 133–143 (2007). https://doi.org/10.1007/s00792-006-0024-3
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DOI: https://doi.org/10.1007/s00792-006-0024-3