Intercepting second-messenger signaling by rationally designed peptides sequestering c-di-GMP
Chee-Seng Hee, Judith Habazettl, Christoph Schmutz, Tilman Schirmer, Urs Jenal, Stephan Grzesiek
Abstract
Significance Cyclic diguanylate (c-di-GMP) regulates a wide range of bacterial cellular functions from biofilm formation to growth and survival. Based on the structural analysis of the complex of c-di-GMP with a bacterial effector protein followed by amino acid sequence optimization, we have developed a short peptide that binds c-di-GMP with nanomolar affinity and high specificity. This provides many opportunities for biotechnological and biomedical applications. In particular, we show that such an endogenously expressed peptide effectively reduces intracellular c-di-GMP and thereby inhibits and even disintegrates biofilms in Pseudomonas aeruginosa .