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

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-PA...

Full description

Saved in:

Bibliographic Details
Published in:	PLoS pathogens Vol. 20; no. 3; p. e1012094
Main Authors:	Anggramukti, Dhira Saraswati, Ishii, Eiji, Pratama, Andre, Al Kadi, Mohamad, Iida, Tetsuya, Kodama, Toshio, Matsuda, Shigeaki
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 27-03-2024 Public Library of Science (PLoS)
Subjects:	Analysis Bacteria Bacterial Proteins - genetics Bacterial Proteins - metabolism Biocompatibility Biology and life sciences Care and treatment Complications and side effects Cytotoxicity Diagnosis Gastroenteritis Gene expression Gene Expression Regulation, Bacterial Genes Genetic aspects Genetic transcription Humans Infections Medicine and Health Sciences Pathogenicity Pathogens Promoter Regions, Genetic Proteins Risk factors Robustness Seafood Secretion Transcription Transcription factors Type III Secretion Systems - genetics Type III Secretion Systems - metabolism Vibrio infections Vibrio Infections - genetics Vibrio Infections - microbiology Vibrio parahaemolyticus Virulence Virulence (Microbiology) Virulence - genetics Virulence factors Virulence Factors - genetics Virulence Factors - metabolism Japan
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1012094