The Legionella pneumophila two-component regulatory systems that participate in the regulation of Icm/Dot effectors
1The George S. Wise Faculty of Life Sciences, Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, 69978, Ramat-Aviv, Tel-Aviv, Israel, gils@tauex.tau.ac.il.
Abstract:
Legionella pneumophila, the causative agent of Legionnaires' disease, actively manipulates intracellular processes to establish a replication niche inside their host cells. The establishment of its replication niche requires a functional Icm/Dot type IV secretion system which translocates about 300 effector proteins into the host cells during infection. This enormous number of effectors should be coordinated at the level of gene expression, in order to be expressed and translocated at the correct time and appropriate amounts. One of the predominant ways in bacteria to regulate virulence gene expression is by the use of two-component systems (TCSs). To date, four TCSs have been shown to be involved in the regulation of Icm/Dot effector-encoding genes: The PmrAB and CpxRA TCSs that directly control, and the LetAS and LqsRS TCSs that indirectly control the level of expression of effector-encoding genes. According to our current knowledge, these four TCSs control the expression of about 70 effector-encoding genes. The regulation by different TCSs divides the effectors into groups of co-regulated effector-encoding genes that are probably co-expressed at a similar time during infection and might perform related functions. In addition, examples of interplay between these TCSs were already reported indicating that they form part of a regulatory network that orchestrates the expression of L. pneumophila effector-encoding genes during infection.
Insights
Legionella pneumophila uses four two-component systems (TCSs) to regulate the expression of hundreds of virulence effector genes. This coordinated gene expression is crucial for establishing infection and requires coordinated timing and amounts of effector proteins.
Area of Science:
- Bacterial pathogenesis
- Molecular microbiology
- Gene regulation
Background:
- Legionella pneumophila causes Legionnaires' disease by manipulating host cells.
- A functional Icm/Dot type IV secretion system is essential for translocating ~300 effector proteins.
- Bacterial virulence gene expression is often regulated by two-component systems (TCSs).
Purpose of the Study:
- To investigate the role of TCSs in regulating L. pneumophila effector protein expression.
- To identify the specific TCSs involved in controlling Icm/Dot effector genes.
- To understand how TCSs coordinate the expression of numerous effector proteins.
Main Methods:
- Analysis of existing literature on TCSs and effector gene regulation in L. pneumophila.
- Identification of TCSs directly and indirectly controlling Icm/Dot effector genes.
- Examination of the interplay between different TCSs.
Main Results:
- Four TCSs (PmrAB, CpxRA, LetAS, LqsRS) are involved in regulating Icm/Dot effector genes.
- These TCSs control the expression of approximately 70 effector genes.
- TCSs group co-regulated effector genes, suggesting coordinated expression and function during infection.
- Interplay between TCSs indicates a complex regulatory network.
Conclusions:
- TCSs are critical for orchestrating the expression of L. pneumophila effector genes.
- Co-regulation by TCSs likely ensures timely and appropriate delivery of effector proteins.
- A regulatory network involving multiple TCSs coordinates virulence factor expression during infection.
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