서강대학교

초록/요약

Quorum sensing and iron response play important roles in regulation of V. vulnificus pathogenesis. To understand quorum sensing pathway in V. vulnificus, We characterized five quorum sensing regulatory sRNAs (Qrrs), which convey quorum sensing signal from LuxO to SmcR: At low cell density, phosphorylated LuxO activates transcription of Qrrs, which inhibit SmcR translation; at high cell density, dephosphorylated LuxO no longer activates Qrrs, resulting in SmcR derepression. Five Qrrs are differentially expressed in response to cell density, but function redundantly to ensure a tight repression of SmcR at low cell density. Iron-responsive regulation and quorum sensing are correlated in V. vulnificus. Iron represses Qrrs through three distinct ways: First, iron-ferric uptake regulator (Fur) complex directly binds to qrrs promoter regions, inhibiting LuxO activation by competing with LuxO for cis-acting elements; Second, qrrs transcription is repressed by iron independently of Fur. Third, LuxO expression is repressed by iron independently of Fur. Qrrs repress SmcR redundantly in iron rich condition while additively in iron limited condition, suggesting that all five Qrrs are necessary for the bacteria. Moreover, RyhB, a small RNA which is expressed at iron limited condition, promotes AI-2 production, resulting in activation of virulence factor, VvpE. Besides, quorum sensing regulator SmcR represses siderophore production through transcriptional repression of vvsAB, which encode a member of the nonribosomal peptide synthase (NRPS) family required for the vulnibactin biosynthesis in V. vulnificus. Fur competes with SmcR to bind the promoter region of vvsAB with higher affinity, resulting in a dominant repression of vvsAB under iron rich condition, while at iron limited condition, quorum sensing elicits a repression of vvsAB at high cell density. These suggest that iron, quorum sensing, and their cognate regulatory circuits are linked together to obtain coordinated expression of virulence factors, and that acquisition of iron in a proper level may be at least one of main purposes of quorum-sensing regulation in this pathogen.