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Nat Med. 2005 Oct;11(10):1082-7. Epub 2005 Oct 2.

Dysregulation of bacterial proteolytic machinery by a new class of antibiotics.

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Department of Anti-infectives, Bayer HealthCare AG, Pharma Research, Aprather Weg 18a, D-42096 Wuppertal, Germany.

Erratum in

  • Nat Med. 2005 Dec;11(12):1361.


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.

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