Fitting Pieces into the Puzzle of Pseudomonas aeruginosa Type III Secretion System Gene Expression

Abstract

Type III secretion systems (T3SS) are widely distributed in Gram-negative microorganisms and critical for host-pathogen and host-symbiont interactions with plants and animals. Central features of the T3SS are a highly conserved set of secretion and translocation genes and contact dependence wherein host-pathogen interactions trigger effector protein delivery and serve as an inducing signal for T3SS gene expression. In addition to these conserved features, there are pathogen-specific properties that include a unique repertoire of effector genes and mechanisms to control T3SS gene expression. The Pseudomonas aeruginosa T3SS serves as a model system to understand transcriptional and posttranscriptional mechanisms involved in the control of T3SS gene expression. The central regulatory feature is a partner-switching system that controls the DNA-binding activity of ExsA, the primary regulator of T3SS gene expression. Superimposed upon the partner-switching mechanism are cyclic AMP and cyclic di-GMP signaling systems, two-component systems, global regulators, and RNA-binding proteins that have positive and negative effects on ExsA transcription and/or synthesis. In the present review, we discuss advances in our understanding of how these regulatory systems orchestrate the activation of T3SS gene expression in the context of acute infections and repression of the T3SS as P. aeruginosa adapts to and colonizes the cystic fibrosis airways.

Keywords: DeaD; ExsA; Pseudomonas aeruginosa; RsmA; Vfr; type III secretion.

FIG 1

The T3SS partner-switching mechanism that controls the DNA-binding activity of ExsA. Negative regulators are in red, and positive regulators are in white.

FIG 2

Map of the T3SS regulatory locus and locations of the P_exsC and P_exsA promoter regions. The binding sites for Vfr (30), Fis (58), and VqsM (57) are boxed. Brackets indicate the MvaT and MvaU binding regions based on ChIP-chip data (78). The P_exsA transcription start site is indicated with a large C, and the −10 region is in red.

FIG 3

Regulatory pathways that control T3SS gene expression. Gene products that stimulate T3SS gene expression are shown in white, while those that inhibit are red. Diguanylate cyclases (DGC) that synthesize c-di-GMP are orange, and phosphodiesterases (PDE) that degrade c-di-GMP are blue. P indicates a histidine kinase or response regulator. Blue lines signify transcriptional regulation, green lines signify posttranscriptional regulation, orange lines signify control of protein activity, purple lines signify enzymatic activity, pink lines signify phosphotransfer activity, and black dashed lines are links with indirect or unknown mechanisms.