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

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