bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 7, 2023
Abstract
The
Legionella
pneumophila
Sde
family
of
translocated
proteins
promotes
host
tubular
endoplasmic
reticulum
(ER)
rearrangements
that
are
tightly
linked
to
phosphoribosyl-ubiquitin
(pR-Ub)
modification
Reticulon
4
(Rtn4).
have
two
additional
activities
unclear
relevance
the
infection
process:
K63
linkage-specific
deubiquitination
and
phosphoribosyl
polyubiquitin
(pR-Ub).
We
show
here
activity
(DUB)
stimulates
ER
while
pR-Ub
protects
replication
vacuole
from
cytosolic
surveillance
by
autophagy.
Loss
DUB
is
lowered
Rtn4,
consistent
with
fueling
production
pR-Ub-Rtn4.
In
parallel,
polyUb,
in
a
region
protein
known
as
isoleucine
patch,
prevents
binding
autophagy
adapter
p62.
An
inability
mutants
modify
polyUb
results
immediate
p62
association,
critical
precursor
autophagic
attack.
ability
WT
block
association
decays
quickly
after
bacterial
infection,
predicted
presence
previously
characterized
L.
effectors
inactivate
remove
polyUb.
sum,
these
accessory
act
stimulate
protect
innate
immune
sensing
temporal
fashion.
The Journal of Cell Biology,
Journal Year:
2024,
Volume and Issue:
223(5)
Published: March 22, 2024
Ubiquitin
regulates
various
cellular
functions
by
posttranslationally
modifying
substrates
with
diverse
ubiquitin
codes.
Recent
discoveries
of
new
chain
topologies,
types
bonds,
and
non-protein
have
substantially
expanded
the
complexity
code.
Here,
we
describe
system
covering
basic
principles
recent
related
to
mechanisms,
technologies,
biological
importance.
Environmental Science and Pollution Research,
Journal Year:
2022,
Volume and Issue:
29(51), P. 76532 - 76542
Published: Sept. 26, 2022
Abstract
An
increase
in
the
number
of
reports
legionellosis
European
Union
and
Economic
Area
have
been
recorded
recent
years.
The
cases
is
significant:
from
6947
2015
to
11,298
2019.
This
alarming
as
genus
Legionella
,
which
comprises
a
large
group
bacteria
inhabiting
various
aquatic
systems,
poses
serious
threat
human
health
life,
since
more
than
20
species
can
cause
legionellosis,
with
L.
pneumophila
being
responsible
for
majority
cases.
ability
colonize
diverse
ecosystems
makes
eradication
these
microorganisms
difficult.
A
detailed
understanding
habitat
may
be
helpful
effective
control
this
pathogen.
paper
provides
an
overview
environments
Europe:
natural
(lakes,
groundwater,
rivers,
compost,
soil)
anthropogenic
(fountains,
air
humidifiers,
water
supply
systems),
role
spp.
nosocomial
infections,
are
potentially
fatal
children,
elderly
immunocompromised
patients.
Graphical
abstract
Autophagy,
Journal Year:
2024,
Volume and Issue:
20(9), P. 1968 - 1983
Published: May 31, 2024
Many
bacterial
pathogens
have
evolved
effective
strategies
to
interfere
with
the
ubiquitination
network
evade
clearance
by
innate
immune
system.
Here,
we
report
that
OTUB1,
one
of
most
abundant
deubiquitinases
(DUBs)
in
mammalian
cells,
is
subjected
both
canonical
and
noncanonical
during
Legionella
pneumophila
infection.
The
effectors
SidC
SdcA
catalyze
OTUB1
at
multiple
lysine
residues,
resulting
its
association
a
Legionella-containing
vacuole.
Lysine
promotes
interactions
between
DEPTOR,
an
inhibitor
MTORC1
pathway,
thus
suppressing
signaling.
inhibition
leads
suppression
host
protein
synthesis
promotion
macroautophagy/autophagy
L.
In
addition,
members
SidE
family
(SidEs)
induce
phosphoribosyl
(PR)-linked
Ser16
Ser18
block
DUB
activity.
levels
serine
are
further
regulated
function
antagonize
activities
SidC,
SidEs,
including
Lem27,
DupA,
DupB,
SidJ
SdjA.
Our
study
reveals
effectors-mediated
complicated
mechanism
regulating
activity
DUB.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 30, 2024
Ubiquitination
is
a
posttranslational
modification
in
eukaryotes
that
plays
significant
role
the
infection
of
intracellular
microbial
pathogens,
such
as
Legionella
pneumophila.
While
Legionella-containing
vacuole
(LCV)
coated
with
ubiquitin
(Ub),
it
avoids
recognition
by
autophagy
adaptors.
Here,
we
report
Sdc
and
Sde
families
effectors
work
together
to
build
ubiquitinated
species
around
LCV.
The
catalyze
canonical
polyubiquitination
directly
on
host
targets
or
phosphoribosyl-Ub
conjugated
Sde.
Remarkably,
Ub
moieties
within
poly-Ub
chains
are
either
modified
phosphoribosyl
group
PDE
domain-containing
covalently
attached
other
substrates
via
Sde-mediated
phosphoribosyl-ubiquitination.
Furthermore,
these
modifications
prevent
adaptors
therefore
exclude
from
In
this
work,
shed
light
nature
poly-ubiquitinated
present
at
surface
LCV
provide
molecular
mechanism
for
avoidance
Ub-decorated
PLoS Pathogens,
Journal Year:
2024,
Volume and Issue:
20(5), P. e1011783 - e1011783
Published: May 13, 2024
Legionella
pneumophila
strains
harboring
wild-type
rpsL
such
as
Lp02
WT
cannot
replicate
in
mouse
bone
marrow-derived
macrophages
(BMDMs)
due
to
induction
of
extensive
lysosome
damage
and
apoptosis.
The
bacterial
factor
directly
responsible
for
inducing
cell
death
the
host
involved
initiating
signaling
cascade
that
leads
remain
unknown.
Similarly,
factors
may
alleviate
induced
by
these
have
not
yet
been
investigated.
Using
a
genome-wide
CRISPR/Cas9
screening,
we
identified
Hmg20a
Nol9
important
restricting
strain
BMDMs.
Depletion
protects
from
infection-induced
lysosomal
apoptosis,
allowing
productive
replication.
restriction
imposed
was
mediated
repressing
expression
several
endo-lysosomal
proteins,
including
small
GTPase
Rab7.
We
found
SUMOylated
Rab7
is
recruited
phagosome
via
SulF,
Dot/Icm
effector
harbors
SUMO-interacting
motif
(SIM).
Moreover,
overexpression
rescues
intracellular
growth
Our
results
establish
L
.
exploits
network
biogenesis
its
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 30, 2024
The
Legionella
pneumophila
Sde
family
of
translocated
proteins
promotes
host
tubular
endoplasmic
reticulum
(ER)
rearrangements
that
are
tightly
linked
to
phosphoribosyl-ubiquitin
(pR-Ub)
modification
Reticulon
4
(Rtn4).
have
two
additional
activities
unclear
relevance
the
infection
process:
K63
linkage-specific
deubiquitination
and
phosphoribosyl
polyubiquitin
(pR-Ub).
We
show
here
activity
(DUB)
stimulates
ER
while
pR-Ub
protects
replication
vacuole
from
cytosolic
surveillance
by
autophagy.
Loss
DUB
is
lowered
Rtn4,
consistent
with
fueling
production
pR-Ub-Rtn4.
In
parallel,
polyUb,
in
a
region
protein
known
as
isoleucine
patch,
prevents
binding
autophagy
adapter
p62.
An
inability
mutants
modify
polyUb
results
immediate
p62
association,
critical
precursor
autophagic
attack.
ability
WT
block
association
decays
quickly
after
bacterial
infection,
predicted
presence
previously
characterized
L.
effectors
inactivate
remove
polyUb.
sum,
these
accessory
act
stimulate
protect
innate
immune
sensing
temporal
fashion.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 18, 2025
Abstract
Legionella
pneumophila
is
an
opportunistic
bacterial
pathogen
that
causes
Legionnaires’
disease.
To
establish
intracellular
niche
conducive
to
replication,
L.
translocates
a
diverse
array
of
effector
proteins
manipulate
various
host
cellular
processes,
including
the
actin
cytoskeleton.
In
screen
for
effectors
alter
dynamics,
we
identified
effector,
Lfat1,
which
colocalizes
with
cytoskeleton
in
eukaryotic
cells.
Lfat1
specifically
binds
F-actin
through
novel
actin-binding
domain
(ABD).
High-resolution
cryo-electron
microscopy
(cryoEM)
analysis
revealed
this
ABD
forms
long
α-helix
hairpin,
its
tip
interacting
subdomains
I
and
II
two
adjacent
molecules
within
filament.
Interestingly,
while
individual
α-helices
hairpin
fail
bind
F-actin,
co-expression
as
separate
fusion
restores
binding
activity.
Furthermore,
demonstrated
exhibits
lysine
fatty-acyltransferase
(KFAT)
activity,
targeting
small
GTPases.
These
findings
foundation
studying
KFAT
family
toxins
uncover
motif,
providing
alternative
marker
notable
flexibility.
Infection and Immunity,
Journal Year:
2023,
Volume and Issue:
91(4)
Published: March 13, 2023
To
replicate
within
host
cells,
bacterial
pathogens
must
acquire
host-derived
nutrients
while
avoiding
degradative
antimicrobial
pathways.
Fundamental
insights
into
pathogenicity
have
been
revealed
by
bacteria
of
the
genus
Legionella,
which
naturally
parasitize
free-living
protozoa
establishing
a
membrane-bound
replicative
niche
termed
Legionella-containing
vacuole
(LCV).
Biogenesis
LCV
and
intracellular
replication
rely
on
rapid
evasion
endocytic
pathway
acquisition
nutrients,
much
is
mediated
effector
proteins
translocated
cells
Dot/Icm
type
IV
secretion
system.
Billions
years
co-evolution
with
eukaryotic
hosts
broad
tropism
resulted
in
expansion
Legionella
genome
to
accommodate
massive
repertoire
that
promote
biogenesis,
safeguard
from
endolysosomal
maturation,
mediate
nutrients.
This
minireview
focused
mechanisms
an
ancient
pathogen
leverages
hijacks
cell
biology
obtain
essential
prevent
lysosomal
degradation.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Nov. 22, 2023
Deubiquitinating
enzymes
(DUBs)
are
emerging
as
key
factors
for
the
infection
of
human
cells
by
pathogens
such
bacteria
and
parasites.
In
this
review,
we
discuss
most
recent
studies
on
role
deubiquitinase
activity
in
exploiting
manipulating
ubiquitin
(Ub)-dependent
host
processes
during
infection.
The
discussed
here
highlight
importance
DUB
host-pathogen
research
underscore
therapeutic
potential
inhibiting
pathogen-specific
to
prevent
infectious
diseases.