dictyNews
Electronic Edition
Volume 35, number 6
September 3, 2010
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Abstracts
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Differential regulation by phosphoinositides of bacterial uptake and
Nramp1
(Slc11a1)-induced resistance to Legionella infection in Dictyostelium
Barbara Peracino, Alessandra Balest and Salvatore Bozzaro
Department of Clinical and Biological Sciences, University of Turin,
AOU S. Luigi, 10043 Orbassano (Torino), Italy
J Cell Science, in press
Membrane phosphatidylinositides recruit cytosolic proteins, regulating
phagocytosis, macropinocytosis and endo-lysosomal vesicle maturation.
Here we describe effects of PI3K, PTEN or PLC inactivation on
Escherichia
coli and Legionella pneumophila uptake by the professional phagocyte
Dictyostelium discoideum. We show that L. pneumophila is engulfed by
macropinocytosis, a process that is partially sensitive, unlike E. coli
phagocytosis, to PI3K inactivation. Both processes are blocked by PLC i
nhibition. While E. coli is rapidly digested, Legionella proliferates
intracellularly. Proliferation is blocked by constitutively expressing
Nramp1,
an endo-lysosomal iron transporter that confers resistance against
invasive
bacteria. Inactivating PI3K, but not PTEN or PLC, enhances Legionella
infection and suppresses the protective effect of Nramp1 overexpression.
PI3K activity is restricted to early infection and is not mediated by
effects
on the actin cytoskeleton, rather L. pneumophila, in contrast to E.
coli,
subverts phosphoinositide-sensitive fusion of Legionella-containing
macropinosomes with acidic vesicles, without affecting Nramp1
recruitment.
A model is presented to explain how Legionella escapes fusion with
acidic
vesicles and Nramp1-induced resistance to pathogens.
Submitted by Salvo Bozzaro [[log in to unmask]]
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