A transcriptional regulatory circuit amplifies virulence gene expression in Vibrio parahaemolyticus (Iida-Lab, PLOS Pathogens)

RIMD researchers elucidate an autoregulatory circuit of a virulence regulator gene expression in Vibrio parahaemolyticus, linked by read-through transcription.

Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis in humans worldwide. This bacterium was first isolated by Tsunesaburo Fujino at RIMD in 1950. The major virulence determinant responsible for the enterotoxicity of this pathogen is the type III secretion system 2 (T3SS2) encoded on the pathogenicity island, the gene expression of which is governed by the transcriptional regulator VtrB.

In this study, the researchers found a positive autoregulatory feature of vtrB transcription, as often seen among the transcriptional regulators of bacteria, but not in a canonical way dependent on its own promoter. They revealed that this autoactivation is mediated by a two-step mechanism: first, VtrB activates the promoter of the VtrB-regulated operon located upstream of vtrB, and second, transcription from the distal promoter overcomes the terminator located upstream of the vtrB gene, resulting in transcription read-through with read-in transcription of the vtrB gene. Furthermore, the perturbation of this read-through transcription impaired T3SS2-associated gene expression and attenuated T3SS2-mediated pathogenicity. Thus, this work offers new insights into how V. parahaemolyticus controls its virulence gene expression to ensure pathogenicity and also provides a framework for further exploring the analogous mechanisms for autoactivation of transcription factor gene expression in bacteria.

RIMD graduate student Dhira Saraswati Anggramukti and RIMD assistant professor Eiji Ishii are the co-lead authors of the paper. Shigeaki Matsuda, an RIMD associate professor, is the senior author of the study.

This article was published in PLOS Pathogens on March 27, 2024.

Title: “The read-through transcription-mediated autoactivation circuit for virulence regulator expression drives robust type III secretion system 2 expression in Vibrio parahaemolyticus”

Authors: Dhira Saraswati Anggramukti^#, Eiji Ishii^#, Andre Pratama, Mohamad Al kadi, Tetsuya Iida, Toshio Kodama, Shigeaki Matsuda* (^#co-lead author, *corresponding author)