Basic studies on design of artificial chemical language compounds for cell-to-cell communication in Gram-negative bacteria.

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Many Gram-negative bacteria communicate with each other by using N-acyl-L-homoserine lactone (AHL) as "chemical language"". This cell-to-cell communication is called quorum sensing. We synthesized a series of AHL analogs and tested them for functioning as "chemical language". It was found that N-acyl-cyclopentylamides show inhibitory effects on quorum sensing in Pseudomonas aeruginosa. N-Decanoylcyclopentylamide (C10-CPA) is the strongest antagonist among N-acylcyclopentylamides synthesized. C10-CPA inhibits production of pathogenic factors including elastase, rhamnolipid, and pyocyanin as well as biofilm formation in P.aeruginosa.. Genetic analysis suggested that C10-CPA inhibits enzymatic activity of LasI, which synthesizes AHL. LasR and RhlR, which are regulatory proteins in quorum sensing, are thought to be important for evaluating synthesized compounds as artificial chemical languages. We successfully overexpressed the lasR and rhlR genes in Escherichia coli and purified them. We also confirmed that purified LasR and RhlR retain the ability to bind to their cognate DNA binding sites.