Revisiting an old antibiotic: bacitracin neutralizes binary bacterial toxins and protects cells from intoxication

• DOI: 10.1096/fj.201802453r
• Publication Date: 2019-01-30T22:08:16Z
• Authors: Leonie Schnell; Ina Felix; Bastian Müller; Mirko Sadi; Franziska Bank; Panagiotis Papath...; Michel R. Popoff; Klaus Aktories; Eva Waltenberger; Roland Benz; Conrad Weichbrodt; Michael Fauler; Manfred Frick; Holger Barth
• Keywords: Anthrax toxin; Bacitracin; Bacillus anthracis

The antibiotic bacitracin (Bac) inhibits cell wall synthesis of gram-positive bacteria. Here, we discovered a totally different activity Bac: the neutralization bacterial exotoxins. Bac prevented intoxication mammalian cells with binary enterotoxins Clostridium botulinum C2, C. perfringens ɩ, difficile transferase (CDT), and Bacillus anihracis lethal toxin. transport (B) subunits these toxins deliver their respective enzyme (A) into cells. Following endocytosis, B form pores in membranes endosomes, which mediate translocation A cytosol. inhibited formation such lipid bilayers vitro living cells, thereby preventing subunit preserved epithelial integrity toxin-treated CaCo-2 monolayers, model for human gut epithelium. In conclusion, should be discussed as therapeutic option against infections medically relevant toxin-producing bacteria, including B. anthracis, because it growth neutralizes secreted toxins.—Schnell, L., Felix, I., Müller, B., Sadi, M., von Bank, F., Papatheodorou, P., Popoff, M. R., Aktories, K., Waltenberger, E., Benz, Weichbrodt, C., Fauler, Frick, Barth, H. Revisiting an old antibiotic: protects from intoxication. FASEB J. 33, 5755–5771 (2019). www.fasebj.org