Global analysis of extracytoplasmic stress signaling in Escherichia coli

Abstract

The Bae, Cpx, Psp, Rcs, and sigma(E) pathways constitute the Escherichia coli signaling systems that detect and respond to alterations of the bacterial envelope. Contributions of these systems to stress response have previously been examined individually; however, the possible interconnections between these pathways are unknown. Here we investigate the dynamics between the five stress response pathways by determining the specificities of each system with respect to signal-inducing conditions, and monitoring global transcriptional changes in response to transient overexpression of each of the effectors. Our studies show that different extracytoplasmic stress conditions elicit a combined response of these pathways. Involvement of the five pathways in the various tested stress conditions is explained by our unexpected finding that transcriptional responses induced by the individual systems show little overlap. The extracytoplasmic stress signaling pathways in E. coli thus regulate mainly complementary functions whose discrete contributions are integrated to mount the full adaptive response.

Figure 1. Transcriptome parallel analysis.

(A) Correlation circle of the principal component analysis. Arrows indicate the different conditions. Principal component axes 3 and 4 are presented. (B) Hierarchical clustering of genes found to be significantly regulated in all the conditions studied by micro-arrays. Bars in red and green indicate genes that are up- and down-regulated, respectively. Color intensities are proportional to the variation of expression.

Figure 2. Venn diagram representation of all five extracytoplasmic response pathways.

The total number of genes/operons (i.e. transcription units; TU) affected in each condition, positive (+) and negative (−) regulation found in the present study, is indicated for each regulon. The Cpx regulon comprises genes affected by CpxR overproduction or deletion (genes repressed or induced by the absence of cpxR are counted + and −, respectively). Only genes that are common to at least two regulons and confirmed by qRT-PCR and/or the literature are listed (red: induced, green: repressed). Genes described in the literature as dependent on CpxR and σ^E or BaeR are also included.