Journal article
Rapid Escape of the dot/icm Mutants of Legionella pneumophila into the Cytosol of Mammalian and Protozoan Cells
Infection and immunity, Vol.75(7), pp.3290-3304
07/2007
Handle:
https://hdl.handle.net/2376/113362
PMCID: PMC1932949
PMID: 17438033
Abstract
The
Legionella pneumophila
-containing phagosome evades endocytic fusion and intercepts endoplasmic reticulum (ER)-to-Golgi vesicle traffic, which is believed to be mediated by the Dot/Icm type IV secretion system. Although phagosomes harboring
dot/icm
mutants are thought to mature through the endosomal-lysosomal pathway, colocalization studies with lysosomal markers have reported contradictory results. In addition, phagosomes harboring the
dot/icm
mutants do not interact with endocytosed materials, which is inconsistent with maturation of the phagosomes in the endosomal-lysosomal pathway. Using multiple strategies, we show that the
dot/icm
mutants defective in the Dot/Icm structural apparatus are unable to maintain the integrity of their phagosomes and escape into the cytoplasm within minutes of entry into various mammalian and protozoan cells in a process independent of the type II secretion system. In contrast, mutants defective in cytoplasmic chaperones of Dot/Icm effectors and
rpoS
,
letA/S
, and
letE
regulatory mutants are all localized within intact phagosomes. Importantly, non-
dot/icm L. pneumophila
mutants whose phagosomes acquire late endosomal-lysosomal markers are all located within intact phagosomes. Using high-resolution electron microscopy, we show that phagosomes harboring the
dot/icm
transporter mutants do not fuse to lysosomes but are free in the cytoplasm. Inhibition of ER-to-Golgi vesicle traffic by brefeldin A does not affect the integrity of the phagosomes harboring the parental strain of
L. pneumophila
. We conclude that the Dot/Icm transporter is involved in maintaining the integrity of the
L. pneumophila
phagosome, independent of interception of ER-to-Golgi vesicle traffic, which is a novel function of type IV secretion systems.
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Details
- Title
- Rapid Escape of the dot/icm Mutants of Legionella pneumophila into the Cytosol of Mammalian and Protozoan Cells
- Creators
- Maëlle Molmeret - Department of Microbiology and Immunology, Room MS-410, University of Louisville College of Medicine, Louisville, Kentucky 40292Marina Santic’ - Department of Microbiology and Immunology, Room MS-410, University of Louisville College of Medicine, Louisville, Kentucky 40292Rexford Asare - Department of Microbiology and Immunology, Room MS-410, University of Louisville College of Medicine, Louisville, Kentucky 40292Reynold A Carabeo - Department of Microbiology and Immunology, Room MS-410, University of Louisville College of Medicine, Louisville, Kentucky 40292Yousef Abu Kwaik - Department of Microbiology and Immunology, Room MS-410, University of Louisville College of Medicine, Louisville, Kentucky 40292
- Publication Details
- Infection and immunity, Vol.75(7), pp.3290-3304
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- American Society for Microbiology
- Identifiers
- 99900548081601842
- Language
- English
- Resource Type
- Journal article