Specific Interactions of Clausin, a New Lantibiotic, with Lipid Precursors of the Bacterial Cell Wall

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• 作者：Ahmed Bouhss ; Bayan Al-Dabbagh ; Michel Vincent ; Benoit Odaert ; Magalie Aumont-Nicaise ; Philippe Bressolier ; Michel Desmadril ; Dominique Mengin-Lecreulx ; Maria C. Urdaci ; Jacques Gallay
• 刊名：Biophysical Journal
• 出版年：2009
• 出版时间：2 September 2009
• 年：2009
• 卷：97
• 期：5
• 页码：1390-1397
• 全文大小：657 K

文摘

We investigated the specificity of interaction of a new type A lantibiotic, clausin, isolated from Bacillus clausii, with lipid intermediates of bacterial envelope biosynthesis pathways. Isothermal calorimetry and steady-state fluorescence anisotropy (with dansylated derivatives) identified peptidoglycan lipids I and II, embedded in dodecylphosphocholine micelles, as potential targets. Complex formation with dissociation constants of 0.3 μM and stoichiometry of 2:1 peptides/lipid intermediate was observed. The interaction is enthalpy-driven. For the first time, to our knowledge, we evidenced the interaction between a lantibiotic and C₅₅-PP-GlcNAc, a lipid intermediate in the biosynthesis of other bacterial cell wall polymers, including teichoic acids. The pyrophosphate moiety of these lipid intermediates was crucial for the interaction because a strong binding with undecaprenyl pyrophosphate, accounting for 80 % of the free energy of binding, was observed. No binding occurred with the undecaprenyl phosphate derivative. The pentapeptide and the N-acetylated sugar moieties strengthened the interaction, but their contributions were weaker than that of the pyrophosphate group. The lantibiotic decreased the mobility of the pentapeptide. Clausin did not interact with the water-soluble UDP-MurNAc- and pyrophosphoryl-MurNAc-pentapeptides, pointing out the importance of the hydrocarbon chain of the lipid target.