Inhibition of Quorum Sensing and Biofilm Formation by Synthetic Quorum Signal Analogues in Pseudomonas aeruginosa.

摘要

Pseudomonas aeruginosa is an opportunistic pathogen that causes various infections on urinary track, cornea, respiratory track, and bum wound site, and mainly relies on quorum sensing (QS) for its virulence. To control the infectivity of P. aeruginosa, we previously synthesized the structural analogues of a major QS signal, N-3-oxododecanoyl homoserine lactone (30C12-HSL) to use as a QS inhibitor. Two of them (5b and 5f) had been confirmed to have an inhibitory effect on LasR, a major QS signal receptor of P. aeruginosa in the screening by the recombinant Escherichia coli reporter. To further evaluate these compounds, we tested their efficacy to control the QS and virulence of P. aeruginosa. Unlike the result from E. coli reporter, both 5b and 5f failed to affect the LasR activity in P. aeruginosa, but instead they selectively affected the activity of QscR, another 30C12-HSL receptor of P. aeruginosa. hiterestingly, their effect on QscR was complex and opposite to what we obtained with E. coli system. Both 5b and 5f enhanced the QscR activity at the low concenfration range (< 10 muM), but high concenfration of 5f (~ 1 mM) strongly inhibited QscR. While 5b and 5f didn't affect the production of proteases, the key virulence factor, they significantly reduced the biofilm fonnation that is important in mediating chronic infections. Especially, 5f inhibited the initial attachment of P. aeruginosa, rather than the biofilm maturation. Based on our results, we suggest that 5f can be applied for an anti-biofilm agent without increasing virulence of P. aeruginosa.