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Applying Live Cell Imaging and Cryo-Electron Tomography to Resolve Spatiotemporal Features of the Legionella pneumophila Dot/Icm Secretion System
Published on: March 10, 2020
The perplexing functions and surprising origins of Legionella pneumophila type IV secretion effectors
Irina S Franco1, Howard A Shuman, Xavier Charpentier
1Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
Abstract:
Only a limited number of bacterial pathogens evade destruction by phagocytic cells such as macrophages. Legionella pneumophila is a Gram-negative gamma-proteobacterial species that can infect and replicate in alveolar macrophages, causing Legionnaires' disease, a severe pneumonia. L. pneumophila uses a complex secretion system to inject host cells with effector proteins capable of disrupting or altering the host cell processes. The L. pneumophila effectors target multiple processes but are essentially aimed at modifying the properties of the L. pneumophila phagosome by altering vesicular trafficking, gradually creating a specialized vacuole in which the bacteria replicate robustly. In nature, L. pneumophila is thought to parasitize free-living protists, which may have selected for traits that promote virulence of L. pneumophila in humans. Indeed, many effector genes encode proteins with eukaryotic domains and are likely to be of protozoan origin. Sustained horizontal gene transfer events within the protozoan niche may have allowed L. pneumophila to become a professional parasite of phagocytes, simultaneously giving rise to its ability to infect macrophages, cells that constitute the first line of cellular defence against bacterial infections.
Insights
Legionella pneumophila bacteria infect human macrophages, causing Legionnaires' disease. This pathogen evolved from protozoa, using effector proteins to survive within host cells.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Background:
- Legionella pneumophila is a Gram-negative bacterium causing Legionnaires' disease, a severe pneumonia.
- It infects and replicates within alveolar macrophages, key phagocytic immune cells.
- Pathogens that evade macrophage destruction pose significant health challenges.
Purpose of the Study:
- To understand the mechanisms by which L. pneumophila infects and survives within macrophages.
- To explore the evolutionary origins of L. pneumophila's virulence factors.
- To investigate how bacterial effector proteins manipulate host cell processes.
Main Methods:
- Analysis of L. pneumophila's secretion system and effector proteins.
- Investigation of host-pathogen interactions at the cellular level.
- Comparative genomics to trace the origin of virulence genes.
Main Results:
- L. pneumophila injects effector proteins into macrophages using a complex secretion system.
- These effectors modify the phagosome, creating a specialized replication vacuole.
- Evidence suggests effector genes are of protozoan origin, acquired through horizontal gene transfer.
- This adaptation allows L. pneumophila to thrive within phagocytes.
Conclusions:
- L. pneumophila has evolved into a professional phagocyte parasite, likely through adaptation in protozoan hosts.
- Its virulence relies on sophisticated manipulation of host vesicular trafficking.
- Understanding these mechanisms is crucial for combating Legionnaires' disease.
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