LuxS/AI-2-Mediated Quorum Sensing In Edwardsiella Tarda

Edwardsiella tarda is a bacterial pathogen that can infect both humans and animals.TX1,an Ed.tarda strain isolated from diseased fish,was found to produce autoinducer 2(AI-2)-like activity that was growth phase dependent and modulated by growth conditions.The gene coding for the AI-2 synthase was cloned from TX1 and designated luxS.LuxS was able to complement the AI-2 mutant phenotype of Escherichia coli strain DH5α.Expression of luxS correlated with AI-2 activity and was increased by glucose and decreased by elevated temperature.The effect of glucose was shown to be mediated through the cAMP-CRP complex,which repressed luxS expression.Overexpression of luxS enhanced AI-2 activity in TX1,whereas disruption of luxS expression by antisense RNA interference(ⅰ) reduced the level of AI-2 activity,(ⅱ) impaired bacterial growth under various conditions,(ⅲ) weakened the expression of genes associated with the typeⅢsecretion system and biofilm formation,and(ⅳ) attenuated bacterial virulence.Addition of exogenous AI-2 was able to complement the deficiencies in the expression of TTSS genes and biofilm production but failed to rescue the growth defects.A small peptide 5411 was designed based on the sequence of luxS.5411 expressed by E.coli DH5αand the commensal strain FP3 could be secreted out of the cells and absorbed by E.tarda.Fish administered with FP3 expressing 5411 showed enhanced resistance against E.tarda infection.Our results(ⅰ) demonstrated that the AI-2 activity in TX1 is controlled at least in part at the level of luxS expression,which in turn is regulated by growth conditions, and that the temporal expression of luxS is essential for optimal bacterial infection and survival;(ⅱ) suggested the existence in E.tarda of a LuxS/AI-2-mediated signal transduction pathway that regulates the production of virulence-associated elements. (ⅲ) suggested that LuxS inhibitory peptides might be used as an effective means to control bacterial infections.