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The roundworm Caenorhabditis elegans survives assaults from pathogenic microbes by chemically modifying small-molecule toxins, a multi-institution research team has found (ACS Chem. Biol., DOI: 10.1021/cb300520u). Frank C. Schroeder of Cornell University, Arthur S. Edison of the University of Florida, and coworkers examined how C. elegans defends itself against two unrelated bacterial toxins, 1-hydroxyphenazine released by Pseudomonas aeruginosa and indole released by Escherichia coli. Both of the chemicals can kill the worm. The researchers found that C. elegans glycosylates the toxins, forming nontoxic derivatives. The worm performs both O-glycosylation and N-glycosylation. In addition, it sometimes goes on to phosphorylate the resulting glycosides. By using nuclear magnetic resonance spectroscopy and mass spectrometry, the researchers identified the multiple toxin metabolites. Understanding the pathway by which these glycosylations occur could lead to inhibitors that improve the efficacy of existing drugs for parasitic roundworm infections, they note.
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