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The biofilm lifestyle mode certainly represents one of the most successful behaviors to facilitate bacterial survival in diverse inhospitable environments. Conversely, the ability of bacteria to develop effective biofilms represents one of the major obstacles in the fight against bacterial infections. In Pseudomonas aeruginosa, the biofilm formation is intimately connected to the quorum sensing (QS) mechanisms, a mode of cell-to-cell communication that allows many bacteria to detect their population density in order to coordinate common actions. In this chapter, we propose an overview (i) on P. aeruginosa QS mechanisms and their implication in biofilm formation, and (ii) on natural products that are known to interfere with these QS mechanisms, subsequently disrupting biofilm formation. The concluding remarks focus on perspectives of these compounds as possible antibiotherapy adjuvants.

Endothelin (ET) is a 21 amino acid peptide produced following the cleavage of its precursor, big ET, by a metalloprotease, the endothelin-converting enzyme (ECE). In the study reported here we determined the minimal peptide sequence of big ET necessary for enzyme recognition and cleavage at the P1-P1' site. Furthermore, we have explored the role of the amino acids found at the boundaries of the cleavage site. To reach these goals. we synthesized a series of fragments, all containing the P1-P1' cleavage site, Trp21-Val22. Following the incubation of peptide fragments with a partly purified bovine ECE preparation and after analyzing the cleavage pattern by high-performance liquid chromatography (HPLC), we were able to identify big ET(18-23) amide as the minimal peptide core recognized and cleaved by the enzyme. This hydrolysis was inhibited by phosphoramidon but not by thiorphan, a characteristic of the ECE metalloprotease. However, none of the shorter peptides was able to inhibit the cleavage of big ET-1 by ECE, suggesting that they are not recognized by the enzyme. Particularly, it appears that aspartic acid 18 is a key residue for the recognition phenomenon. The delineation of the minimal structure will be a useful tool to further characterize ECE.