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Evidence for pore-forming ability by Legionella pneumophila
J E Kirby1, J P Vogel, H L Andrews
1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.
Molecular Microbiology
|March 4, 1998
Summary
Legionella pneumophila causes cell lysis by forming a pore in host cell membranes. This pore formation, dependent on specific bacterial genes, aids in bacterial replication within macrophages.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Background:
- Legionella pneumophila is an intracellular bacterium responsible for Legionnaires' pneumonia.
- Upon macrophage internalization, it disrupts normal endocytic pathways, creating a unique replicative vacuole derived from the endoplasmic reticulum.
Purpose of the Study:
- To investigate the mechanism of host cell lysis induced by Legionella pneumophila.
- To determine the role of bacterial factors and pore formation in cytotoxicity and vacuole establishment.
Main Methods:
- Genetic analysis using dotA mutants and other loci.
- Macrophage and red blood cell lysis assays.
- Osmoprotection studies using polyethylene glycols.
- Uptake assays with fluorescent compounds of varying sizes.
Main Results:
- Lysis of host cells by L. pneumophila was dependent on dotA and other genes essential for phagosome targeting and replication.
- Cytotoxicity occurred rapidly during high-multiplicity infections and required close bacterial-host cell association.
- Osmotic lysis, consistent with pore formation (<3 nm diameter), was observed.
- Evidence suggested L. pneumophila can form a pore in eukaryotic membranes upon initial contact.
Conclusions:
- Legionella pneumophila induces necrotic cell death via osmotic lysis, likely through pore formation in the host plasma membrane.
- This pore-forming ability may contribute to altering host cell endocytic trafficking and establishing the replicative vacuole.