Pathogenic Mechanisms of Legionella pneumophila Infections

Legionella pneumophila thrives in aquatic environments within protozoan hosts and enters the human lung following inhalation of contaminated aerosols. Once internalised by alveolar macrophages, the bacterium deploys a Dot/Icm type IV secretion system to inject over 300 effector proteins that hijack key host pathways. These effectors collaboratively remodel the phagosomal membrane into a replicative Legionella-containing vacuole (LCV), subverting endosomal trafficking, modulating phosphoinositide lipids and preventing lysosomal fusion. Noncanonical ubiquitination by SidE-family ligases and its antagonism by Dup deubiquitinases enables dynamic control of host ubiquitin signalling. Other effectors, such as glycosyltransferases of the Lgt family, shut down host protein synthesis and blunt unfolded protein stress responses, whilst proteins targeting host vacuolar H+-ATPases maintain a neutral pH within the LCV. Further layers of regulation are provided by metaeffectors that temporally govern effector activity, ensuring optimal intracellular replication. Immune evasion is achieved through modulation of NF-κB–dependent transcription and interference with antigen presentation. Together, these pathogenic mechanisms underlie Legionnaires’ disease, a severe pneumonia with significant global health impact.

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Pathogenic Mechanisms of Legionella pneumophila Infections publication trend

The graph below shows the total number of articles in pathogenic mechanisms of legionella pneumophila infections across all publications each year (not limited to Nature Index journals).

Technical terms

Dot/Icm type IV secretion system: A multisubunit bacterial apparatus that injects effector proteins across host cell membranes.

Effector protein: A bacterial-secreted factor that modulates host cell functions to favour intracellular survival.

Legionella-containing vacuole (LCV): A specialised membrane-bound compartment derived from the host endoplasmic reticulum in which the bacterium replicates.

Phosphoribosyl ubiquitination: A noncanonical form of ubiquitin modification in which ubiquitin is linked to serine residues via a phosphoribosyl bridge.

Glycosyltransferase: An enzyme that catalyses transfer of sugar moieties from activated donor molecules to specific substrate proteins.

References

1. Covalent Probes To Capture Legionella pneumophila Dup Effector Enzymes. Journal of the American Chemical Society (2024).
2. Structural Basis for the Action Mechanism of Legionella Glycosyltransferase. Small Structures (2023).
3. Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector. PLOS Pathogens (2010).
4. From Many Hosts, One Accidental Pathogen: The Diverse Protozoan Hosts of Legionella. Frontiers in Cellular and Infection Microbiology (2017).
5. Comprehensive Identification of Protein Substrates of the Dot/Icm Type IV Transporter of Legionella pneumophila. PLOS ONE (2011).
6. Secreted Bacterial Effectors That Inhibit Host Protein Synthesis Are Critical for Induction of the Innate Immune Response to Virulent Legionella pneumophila. PLOS Pathogens (2011).
7. Diverse mechanisms of metaeffector activity in an intracellular bacterial pathogen, Legionella pneumophila. Molecular Systems Biology (2016).
8. Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DupA and DupB. Molecular Cell (2019).
9. Legionella pneumophila Exploits PI(4)P to Anchor Secreted Effector Proteins to the Replicative Vacuole. PLOS Pathogens (2006).
10. Legionella Eukaryotic-Like Type IV Substrates Interfere with Organelle Trafficking. PLOS Pathogens (2008).