Regulatory network features in Listeria monocytogenes-changing the way we talk

Abstract

Our understanding of how pathogens shape their gene expression profiles in response to environmental changes is ever growing. Advances in Bioinformatics have made it possible to model complex systems and integrate data from variable sources into one large regulatory network. In these analyses, regulatory networks are typically broken down into regulatory motifs such as feed-forward loops (FFL) or auto-regulatory feedbacks, which serves to simplify the structure, while the functional implications of different regulatory motifs allow to make informed assumptions about the function of a specific regulatory pathway. Here we review the basic concepts of network features and use this language to break down the regulatory networks that govern the interactions between the main regulators of stress response, virulence, and transmission in Listeria monocytogenes. We point out the advantage that taking a "systems approach" could have for our understanding of gene functions, the detection of distant regulatory inputs, interspecies comparisons, and co-expression.

Keywords: Listeria monocytogenes; PrfA; SigB; network motif; regulatory network.

Figure 1

Regulatory features. Proteins “X” and “W” are positive regulators, proteins “Y” and “Q” are negative regulators and protein “Z” is a non-regulator. All six motifs represented can be recognized in L. monocytogenes (see Figure 2).

Figure 2

Regulatory features in L. monocytogenes. The regulatory network involves six transcriptional regulators; the alternative σ factors σ^B and σ^L, the transcription activators PrfA and ManR, and the transcription repressors CtsR and NagR (blue squares). Proteins not involved in transcription regulation are enclosed in hexagons. Proteins mostly active during environmental growth (green) include NagA, an N-acetyl-glucosamine-6-phosphate deacetylase, NagB, a glucosamine-6-phosphate deaminase, PTS^Mpo and PTS^Man, two glucose PTSs; ClpC, a protease, InlA and InlB, two internalin proteins, and Bsh, a bile salt hydrolase, are involved in the early stages of infection (yellow); ClpP is a serine protease and Hly, Mpl, PlcA, PlcB, and ActA are virulence factors involved in the intracellular stage of infection (red). SreA is a trans-acting noncoding RNA. Solid arrows () indicate activation and crossed lines () indicate repression. Solid black lines indicate transcriptional regulation (i.e., regulation at the DNA level); dotted black lines indicate post-transcriptional regulation (i.e., regulation at the RNA level); dashed black lines indicate post-translational regulation (i.e., regulation at the protein level); red solid lines indicates unknown mechanism of regulation (i.e., transcriptional, post-transcriptional, or post-translational). The complex regulatory system is broken down into simpler regulatory features as described in the text.