Title

Insights into Transcriptional Silencing and Anti-silencing in Shigella flexneri: A Detailed Molecular Analysis of the icsP Virulence Locus

Document Type

Article

Publication Date

2-17-2018

Publication Title

Molecular Microbiology

Volume

108

Issue

5

First page number:

505

Last page number:

518

Abstract

Transcriptional silencing and anti‐silencing mechanisms modulate bacterial physiology and virulence in many human pathogens. In Shigella species, many virulence plasmid genes are silenced by the histone‐like nucleoid structuring protein H‐NS and anti‐silenced by the virulence gene regulator VirB. Despite the key role that these regulatory proteins play in Shigella virulence, their mechanisms of transcriptional control remain poorly understood. Here, we characterize the regulatory elements and their relative spacing requirements needed for the transcriptional silencing and anti‐silencing of icsP, a locus that requires remotely located regulatory elements for both types of transcriptional control. Our findings highlight the flexibility of the regulatory elements' positions with respect to each other, and yet, a molecular roadblock docked between the VirB binding site and the upstream H‐NS binding region abolishes transcriptional anti‐silencing by VirB, providing insight into transcriptional anti‐silencing. Our study also raises the need to re‐evaluate the currently proposed VirB binding site. Models of transcriptional silencing and anti‐silencing at this genetic locus are presented, and the implications for understanding these regulatory mechanisms in bacteria are discussed.

Disciplines

Microbiology

Language

English

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