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Legionella pneumophila Dot/Icm translocated substrates: a sum of parts
Alexander W Ensminger1, Ralph R Isberg
1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
Abstract:
Legionella pneumophila is an intracellular pathogen of freshwater amoeba and of alveolar macrophages in human hosts. After phagocytosis, L. pneumophila establishes a unique intracellular vacuolar niche that avoids entry into the lysosomal network. Critical for L. pneumophila intracellular growth is the Dot/Icm type IVB translocation system. Although over 80 substrates of the Dot/Icm apparatus have been identified, individual substrates are often genetically redundant, complicating their analysis. Deletion of critical Dot/Icm translocation system components causes a variety of defects during intracellular growth. Many of these effects on the host cell likely result from the actions of one or more Dot/Icm translocated substrates. Loss of single substrates never generates the profound effects observed in strains lacking translocation system components.
Insights
Legionella pneumophila uses the Dot/Icm type IVB system to survive within host cells. While many Dot/Icm substrates exist, individual losses don't replicate the severe effects seen when the entire system is removed.
Area of Science:
- Microbiology
- Cell Biology
- Pathogen-Host Interactions
Background:
- Legionella pneumophila is an intracellular pathogen that infects amoeba and human macrophages.
- Successful intracellular growth depends on establishing a unique vacuolar niche, avoiding lysosomal degradation.
- The Dot/Icm type IVB translocation system is essential for L. pneumophila's intracellular survival and replication.
Purpose of the Study:
- To investigate the role of the Dot/Icm translocation system and its substrates in L. pneumophila pathogenesis.
- To understand how Dot/Icm substrates contribute to the intracellular lifestyle of L. pneumophila within host cells.
- To analyze the functional redundancy and individual contributions of Dot/Icm substrates.
Main Methods:
- Genetic analysis of Dot/Icm translocation system components and their substrates.
- Phenotypic characterization of L. pneumophila mutants within host cells (e.g., amoeba, macrophages).
- Assessment of vacuolar niche formation and intracellular growth.
Main Results:
- Over 80 Dot/Icm substrates have been identified, but many exhibit genetic redundancy.
- Deletion of the entire Dot/Icm system leads to severe intracellular growth defects.
- Loss of single Dot/Icm substrates does not fully replicate the defects observed upon complete system deletion, suggesting complex functional interactions.
Conclusions:
- The Dot/Icm translocation system is indispensable for L. pneumophila's intracellular pathogenesis.
- The collective action of multiple Dot/Icm substrates, rather than individual ones, is critical for overcoming host defenses and establishing a replicative niche.
- Further research is needed to elucidate the specific roles and interplay of individual Dot/Icm substrates in host cell manipulation.
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