Death By Reduction

The human innate immune system produces antimicrobial peptides that keep the trillions of microbes that cohabit peoples' bodies in check. Now, researchers led by Jan Wehkamp of the Institute for Clinical Pharmacology, in Stuttgart, Germany, report that one of these peptides—β-defensin 1, long thought to be feebly antimicrobial—becomes a deadly weapon against microbes when its cysteine residues are reduced (Nature, DOI: 10.1038/nature09674).

This short peptide is copiously produced by human epithelial cells, particularly those in the gut, where many bacteria live and where conditions are anaerobic and therefore reducing. Previously, β-defensin 1's activity had only been studied in oxygen-rich aerobic conditions. Wehkamp’s team found that when the peptide's three cysteine bridges are broken in anaerobic and reducing conditions, the molecule becomes a potent killer of Gram-positive bacteria and fungi. This new route for enhancing antibiotic activity could aid the development of other antibacterial agents as well.

Robert I. Lehrer, a medical researcher at the University of Califonia, Los Angeles, comments in Nature hat the "drastically" changed activity of the reduced β-defensin 1 peptides appears to be inducing the bacteria to self-destruct (DOI: 10.1038/469309a).

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