Conference 2021 Live Talk

 

Talk title

Transcriptional silencing by TsrA in the evolution of pathogenic Vibrio cholerae biotypes

 

Authors and Affiliations

Florence Caro1, José A. Caro2, Nicole M. Place3, John J. Mekalanos1*

1. Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
2. Department of Biochemistry and Biophysics, Texas A&M University, 400 Bizzell St, College Station, TX 77843, USA.
3. Department of Microbial Pathogenesis, Yale School of Medicine, 295 Congress Ave., New Haven, CT 06519, USA.

 

Abstract

Background

Vibrio cholerae is a globally important pathogen responsible for the severe epidemic diarrheal disease called cholera. The current and ongoing seventh pandemic of cholera is caused by El Tor strains which have completely replaced the sixth pandemic classical strains of V. cholerae. To successfully establish infection and disseminate to new victims, V. cholerae relies on key virulence factors encoded on horizontally acquired genetic elements. The expression of these factors relies on the regulatory architecture that coordinates the timely expression of virulence determinants during host infection.

Methods

Here we apply transcriptomics and structural modelling to understand how the type VI secretion system regulator A (TsrA) affects gene expression in both V. cholerae classical and El Tor biotypes.

Results

We find that TsrA acts as a negative regulator of V. cholerae virulence genes encoded on horizontally acquired genetic elements. The TsrA regulon comprises genes encoding cholera toxin (CT), the toxin co-regulated pilus (TCP), the type VI secretion system (T6SS), as well as those involved in biofilm formation. The majority of the TsrA regulon is encoded on horizontally acquired AT-rich genetic islands whose loss or acquisition could be directly ascribed to the differences between the classical and El Tor strains studied. Our modelling predicts that the TsrA protein is a structural homolog of the histone-like nucleoid structuring protein (H-NS) oligomerization domain and likely capable of forming higher order superhelical structures potentially with DNA.

Conclusions

These findings describe how TsrA can integrate into the intricate V. cholerae virulence gene expression program controlling gene expression through transcriptional silencing.