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Fatal attraction of mammalian cells to Legionella pneumophila
1Department of Microbiology and Immunology, University of Kentucky Chandler Medical Center, Lexington 40536-0084, USA. yabukw@pop.uky.edu
Abstract:
Legionella pneumophila is a protozoan parasite that causes Legionnaires' disease. Its ability to do so is dependent on its capacity to replicate intracellularly within a phagosome that is not trafficked through the endosomal-lysosomal pathway and is surrounded by the rough endoplasmic reticulum. Within this unique niche, the bacterium undergoes alterations in gene expression. In addition, many virulence-related phenotypes that are induced in vitro by starvation are expressed intracellularly as the bacteria exit the logarithmic growth phase. (p)ppGpp appears to signal expression of the virulence-related genes in L. pneumophila upon starvation. This growth phase-dependent phenotypical transition is concomitant with lysis of the host cell, in which both necrosis and apoptosis seem to play roles. Many genetic loci that are required for intracellular replication within mammalian and protozoan cells have been identified, and the majority of them are novel. Two secretion systems have been identified, one of which may be distantly related to type IV secretion systems. The other is a type II secretion system similar to the PilBCD piliation system of Pseudomonas aeruginosa.
Insights
Legionella pneumophila causes Legionnaires' disease by replicating inside host cells. Its intracellular survival and virulence depend on specific gene expression and secretion systems, crucial for pathogenesis.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Legionella pneumophila is an intracellular bacterium responsible for Legionnaires' disease.
- Intracellular replication occurs in a unique phagosome, avoiding lysosomal degradation.
- Bacterial gene expression and virulence factors are critical for intracellular survival.
Purpose of the Study:
- To investigate the mechanisms of intracellular replication and virulence in Legionella pneumophila.
- To identify genetic loci and secretion systems involved in host-pathogen interactions.
- To understand the role of growth phase and starvation in virulence gene expression.
Main Methods:
- Analysis of bacterial gene expression during intracellular growth.
- Identification of genetic requirements for intracellular replication in host cells.
- Characterization of bacterial secretion systems.
Main Results:
- Legionella pneumophila replicates within a specialized vacuole, evading the host's endosomal-lysosomal pathway.
- Starvation induces virulence gene expression via (p)ppGpp signaling, correlating with exit from logarithmic growth.
- Novel genetic loci and two distinct secretion systems (one potentially related to Type IV, another a Type II system) were identified.
Conclusions:
- Intracellular replication and virulence of Legionella pneumophila are tightly regulated by growth phase and environmental cues like starvation.
- The identified genetic loci and secretion systems are essential for pathogenesis and represent potential therapeutic targets.
- Understanding these mechanisms provides insights into host-pathogen interactions and disease development.