부산대학교 도서관

Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis in humans worldwide. The major virulence factor responsible for the enteropathogenicity of this pathogen is type III secretion system 2 (T3SS2), which is encoded on the 80-kb V. parahaemolyticus pathogenicity island (Vp-PAI), the gene expression of which is governed by the OmpR-family transcriptional regulator VtrB. Here, we found a positive autoregulatory feature of vtrB transcription, which is often observed with transcriptional regulators of bacteria, but the regulation was not canonically dependent on its own promoter. Instead, this autoactivation was induced by heterogeneous transcripts derived from the VtrB-regulated operon upstream of vtrB. VtrB-activated transcription overcame the intrinsic terminator downstream of the operon, resulting in transcription read-through with read-in transcription of the vtrB gene and thus completing the autoregulatory loop for vtrB gene expression. The dampening of read-through transcription with an exogenous strong terminator reduced vtrB gene expression. Furthermore, a V. parahaemolyticus mutant with defects in the vtrB autoregulatory loop also showed compromises in T3SS2 expression and T3SS2-dependent cytotoxicity in vitro and enterotoxicity in vivo, indicating that this autoregulatory loop is essential for sustained vtrB activation and the consequent robust expression of T3SS2 genes for pathogenicity. Taken together, these findings demonstrate that the regulatory loop for vtrB gene expression based on read-through transcription from the upstream operon is a crucial pathway in T3SS2 gene regulatory network to ensure T3SS2-mediated virulence of V. parahaemolyticus. Author summary: Many bacterial transcription factors undergo autoregulation, a process by which transcription factors regulate their own transcription to amplify or reduce the output responses to a changing environment. The common mode of such autoregulation is achieved by the transcription factor acting on its own promoter. In this study, we found that VtrB, a virulence regulator of the T3SS2 genes of the major food-borne pathogen Vibrio parahaemolyticus, autoregulates its own expression but independently of its own promoter. We also demonstrated how this autoregulation occurs: VtrB activates transcription of the upstream operon and transcription extends to the vtrB gene over the relatively less effective intrinsic terminator. Read-through transcription thus underlies the autoregulatory loop of vtrB expression. Moreover, this autoregulation was essential for the amplification of V. parahaemolyticus T3SS2 expression and induction of the full virulence of this pathogen. Together, our findings not only offer new insights into how V. parahaemolyticus controls its virulence gene expression to ensure pathogenicity but also provide a framework for further exploring the analogous mechanisms for the autoactivation of transcription factor gene expression in bacteria. [ABSTRACT FROM AUTHOR]