A Regulatory Network Controls cabABC Expression Leading to Biofilm and Rugose Colony Development in Vibrio vulnificus

Abstract

Biofilms provide bacteria with protection from environmental stresses and host immune defenses. The pathogenic marine bacterium <i>Vibrio vulnificus</i> forms biofilms and colonizes environmental niches such as oysters. The <i>cabABC</i> operon encodes an extracellular matrix protein CabA and the corresponding type I secretion system, which are essential for biofilm and rugose colony development of <i>V. vulnificus</i>. In this study, molecular biological analyses revealed the roles of three transcriptional regulators BrpR, BrpT, and BrpS in the regulatory pathway for the <i>cabABC</i> operon. BrpR induces <i>brpT</i> and BrpT in turn activates the <i>cabABC</i> operon in a sequential cascade, contributing to development of robust biofilm structures. BrpT also activates <i>brpS</i>, but BrpS represses <i>brpT</i>, constituting a negative feedback loop that stabilizes <i>brpT</i> expression. BrpT and BrpS directly bind to specific sequences upstream of <i>cabA</i>, and they constitute a feedforward loop in which BrpT induces <i>brpS</i> and together with BrpS activates <i>cabABC</i>, leading to precise regulation of <i>cabABC</i> expression. Accordingly, BrpS as well as BrpT plays a crucial role in complete development of rugose colonies. This elaborate network of three transcriptional regulators BrpR, BrpT, and BrpS thus tightly controls <i>cabABC</i> regulation, and contributes to successful development of robust biofilms and rugose colonies in <i>V. vulnificus</i>.