Author: ["Heike Brötz-Oesterhelt","Dieter Beyer","Hein-Peter Kroll","Rainer Endermann","Christoph Ladel","Werner Schroeder","Berthold Hinzen","Siegfried Raddatz","Holger Paulsen","Kerstin Henninger","Julia E Bandow","Hans-Georg Sahl","Harald Labischinski"]
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Abstract
Here we show that a new class of antibiotics—acyldepsipeptides—has antibacterial activity against Gram-positive bacteria in vitro and in several rodent models of bacterial infection. The acyldepsipeptides are active against isolates that are resistant to antibiotics in clinical application, implying a new target, which we identify as ClpP, the core unit of a major bacterial protease complex. ClpP is usually tightly regulated and strictly requires a member of the family of Clp-ATPases and often further accessory proteins for proteolytic activation. Binding of acyldepsipeptides to ClpP eliminates these safeguards. The acyldepsipeptide-activated ClpP core is capable of proteolytic degradation in the absence of the regulatory Clp-ATPases. Such uncontrolled proteolysis leads to inhibition of bacterial cell division and eventually cell death.Cite this article
Brötz-Oesterhelt, H., Beyer, D., Kroll, HP. et al. Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nat Med 11, 1082–1087 (2005). https://doi.org/10.1038/nm1306 