bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Feb. 6, 2023
(Cb)
is
an
obligate
intracellular
pathogen
in
nature
and
the
causative
agent
of
acute
Q
fever
as
well
chronic
diseases.
In
effort
to
identify
genes
proteins
crucial
their
normal
growth
lifestyle,
we
applied
a
"Reverse
evolution"
approach
where
avirulent
Nine
Mile
Phase
II
strain
Cb
was
grown
for
67
passages
chemically
defined
ACCM-D
media
gene
expression
patterns
genome
integrity
from
various
compared
passage
number
one
following
growth.
Transcriptomic
analysis
identified
marked
downregulation
structural
components
type
4B
secretion
system
(T4BSS),
general
secretory
(sec)
pathway,
14
out
118
previously
encoding
effector
proteins.
Additional
downregulated
pathogenicity
determinants
included
several
chaperones,
LPS,
peptidoglycan
biosynthesis.
A
central
metabolic
pathways
also
observed,
which
balanced
by
upregulation
transporters.
This
pattern
reflected
richness
diminishing
anabolic
ATP-generation
needs.
Finally,
genomic
sequencing
comparative
demonstrated
extremely
low
level
mutation
across
passages,
despite
observed
changes
acclimation
axenic
media.
PLoS Pathogens,
Journal Year:
2022,
Volume and Issue:
18(7), P. e1010660 - e1010660
Published: July 11, 2022
Coxiella
burnetii
is
the
etiological
agent
of
zoonotic
disease
Q
fever,
which
featured
by
its
ability
to
replicate
in
acid
vacuoles
resembling
lysosomal
network.
One
key
virulence
determinant
C.
Dot/Icm
system
that
transfers
more
than
150
effector
proteins
into
host
cells.
These
effectors
function
construct
lysosome-like
compartment
permissive
for
bacterial
replication,
but
functions
most
these
remain
elusive.
In
this
study,
we
used
an
affinity
tag
purification
mass
spectrometry
(AP-MS)
approach
generate
a
burnetii-human
protein-protein
interaction
(PPI)
map
involving
53
and
3480
proteins.
This
PPI
revealed
CBU0425
(designated
CirB)
interacts
with
subunits
20S
core
proteasome.
We
found
ectopically
expressed
CirB
inhibits
hydrolytic
activity
addition,
overexpression
caused
dramatic
inhibition
proteasome
cells,
while
knocking
down
expression
alleviated
such
inhibitory
effects.
Moreover,
showed
region
spans
residues
91-120
binds
subunit
PSMB5
(beta
5).
Finally,
knockdown
promotes
virulence,
highlighting
importance
modulation
during
course
infection.
International Journal of Medical Microbiology,
Journal Year:
2023,
Volume and Issue:
313(6), P. 151590 - 151590
Published: Nov. 1, 2023
The
Q-GAPS
(Q
fever
GermAn
interdisciplinary
Program
for
reSearch)
consortium
was
launched
in
2017
as
a
German
of
more
than
20
scientists
with
exceptional
expertise,
competence,
and
substantial
knowledge
the
field
Q
pathogen
Coxiella
(C.)
burnetii.
C.
burnetii
exemplifies
zoonotic
challenges
disease
control
prophylaxis
human,
animal,
environmental
settings
One
Health
approach.
An
approach
to
studying
is
essential
address
unresolved
questions
about
epidemiology,
immunology,
pathogenesis,
surveillance,
In
five
years,
has
provided
new
insights
into
pathogenicity
interaction
host
defense
mechanisms.
also
investigated
vaccine
efficacy
application
animal
reservoirs
identified
expanded
phenotypic
genotypic
characteristics
their
epidemiological
significance.
addition,
conceptual
principles
controlling,
surveilling,
preventing
infections
were
developed
prepared
specific
target
groups.
All
findings
have
been
continuously
integrated
Web-based,
interactive,
freely
accessible
information
platform
(www.q-gaps.de),
which
contains
guidelines
support
public
health
institutions
controlling
fever.
this
review,
we
will
summarize
our
results
show
an
example
how
provides
better
tools
at
national
level.
Infection and Immunity,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 12, 2025
ABSTRACT
Coxiella
burnetii
is
a
gram-negative,
obligate
intracellular
pathogen
that
causes
human
Q
fever.
Within
host
cells,
C.
proliferates
in
spacious,
acidic,
lysosome-derived
-containing
vacuole
(CCV)
by
process
requires
the
Dot/Icm
type
IVB
secretion
system
to
deliver
effectors
manipulate
cell
functions.
A
previous
transposon
mutagenesis
screen
identified
gene
cbu0937
as
being
important
for
replication
of
.
Here,
function
Cbu0937
was
investigated.
The
::Tn
mutant
had
no
detectable
defect
replicating
axenic
acidified
citrate
cysteine
medium
2.
Additionally,
not
restored
co-infection
cells
with
an
isogenic
wild-type
strain
Thus,
has
cell-intrinsic
defect.
Intracellular
complementing
trans
plasmid
encoding
either
untagged
or
epitope-tagged
version
Cbu0937.
Analysis
predicted
structure
protein
using
AlphaFold
revealed
high
similarity
between
and
several
bacterial
porins.
Fractionation
studies
surface
labeling
producing
functional
indicated
localization
outer
membrane.
From
these
data,
we
conclude
encodes
porin
plays
essential
role
supporting
replication,
which
likely
involves
acquisition
metabolite
CCV
lumen.
mBio,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 20, 2025
ABSTRACT
Viruses
and
bacteria
exploit
the
nuclear
pore
complex
(NPC)
host
functions
to
bypass
cellular
barriers
manipulate
essential
processes.
frequently
engage
directly
with
NPC
components,
such
as
nucleoporins,
enable
genome
import
evade
immune
defenses.
In
contrast,
bacterial
pathogens
rely
on
secreted
effector
proteins
disrupt
transport
reprogram
transcription.
These
strategies
reflect
a
remarkable
evolutionary
convergence,
both
types
of
targeting
promote
infection.
This
minireview
explores
overlapping
unique
mechanisms
by
which
hijack
nucleus,
shedding
light
their
roles
in
disease
potential
avenues
for
therapeutic
intervention.
Frontiers in Molecular Biosciences,
Journal Year:
2023,
Volume and Issue:
10
Published: March 27, 2023
The
7SK
ribonucleoprotein
(RNP)
is
a
dynamic
and
multifunctional
regulator
of
RNA
Polymerase
II
(RNAPII)
transcription
in
metazoa.
Comprised
the
non-coding
RNA,
core
proteins,
numerous
accessory
most
well-known
RNP
function
sequestration
inactivation
positive
elongation
factor
b
(P-TEFb).
More
recently,
has
been
shown
to
regulate
RNAPII
through
P-TEFb-independent
pathways.
Due
its
fundamental
role
cellular
function,
dysregulation
linked
with
human
diseases
including
cancers,
heart
disease,
developmental
disorders,
viral
infection.
Significant
advances
structural
biology
have
improved
our
understanding
assembly
function.
Here,
we
review
progress
basis
folding,
biogenesis,
assembly.
Frontiers in Microbiology,
Journal Year:
2024,
Volume and Issue:
15
Published: March 14, 2024
Introduction
Plant
bacterial
wilt
is
an
important
worldwide
disease
caused
by
Ralstonia
solanacearum
which
a
complex
of
species.
Methods
In
this
study,
we
identified
and
sequenced
the
genome
R.
strain
gd-2
isolated
from
tobacco.
Results
Strain
was
as
species
(RSSC)
phylotype
I
sequevar
15
exhibited
strong
pathogenicity
to
The
size
5.93
Mb,
including
chromosomes
(3.83
Mb)
megaplasmid
(2.10
Mb).
Gene
prediction
results
showed
that
3,434
1,640
genes
were
in
plasmids,
respectively.
Comparative
genomic
analysis
high
conservation
with
ten
highly
similar
genomes
differences
between
other
mainly
located
at
positions
GI12-GI14.
72
type
III
effectors
(T3Es)
RipAZ2
T3E
specific
compared
eight
strain.
Discussion
Our
study
provides
new
basis
evidence
for
studying
pathogenic
mechanism
.
Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(36)
Published: Aug. 28, 2023
The
causative
agent
of
human
Q
fever,
Coxiella
burnetii,
is
highly
adapted
to
infect
alveolar
macrophages
by
inhibiting
a
range
host
responses
infection.
Despite
the
clinical
and
biological
importance
this
pathogen,
challenges
related
genetic
manipulation
both
C.
burnetii
have
limited
our
knowledge
mechanisms
which
subverts
functions.
Here,
we
used
bacterium
Legionella
pneumophila
perform
comprehensive
screen
effectors
that
interfere
with
innate
immune
death
using
greater
wax
moth
Galleria
mellonella
mouse
bone
marrow–derived
macrophages.
We
identified
MceF
(Mitochondrial
effector
protein
F),
localizes
mitochondria
contributes
cell
survival.
was
shown
enhance
mitochondrial
function,
delay
membrane
damage,
decrease
ROS
production
induced
rotenone.
Mechanistically,
recruits
antioxidant
Glutathione
Peroxidase
4
(GPX4)
mitochondria.
protective
functions
were
absent
in
primary
lacking
GPX4,
while
overexpression
cells
protected
against
oxidative
stress–induced
death.
replication
competent
mammalian
but
higher
mortality
G.
mellonella,
indicating
modulates
response
This
study
reveals
an
important
strategy
subvert
macrophage
immunity
demonstrates
modulation
system
viable
promote
success
intracellular
bacteria.
Molecular Microbiology,
Journal Year:
2023,
Volume and Issue:
121(3), P. 513 - 528
Published: Dec. 19, 2023
Intracellular
bacteria
have
evolved
mechanisms
to
invade
host
cells,
establish
an
intracellular
niche
that
allows
survival
and
replication,
produce
progeny,
exit
the
cell
after
completion
of
replication
cycle
infect
new
target
cells.
Bacteria
their
by
(i)
initiation
apoptosis,
(ii)
lytic
death,
(iii)
exocytosis.
While
bacterial
egress
is
essential
for
spreading
and,
thus,
pathogenesis,
we
currently
lack
information
about
obligate
pathogen
C.
burnetii,
causative
agent
zoonosis
Q
fever.
Here,
demonstrate
burnetii
inhibits
apoptosis
early
during
infection,
but
induces
and/or
increases
at
later
stages
infection.
Only
infection
did
observe
egress,
which
depends
on
previously
established
large
bacteria-filled
vacuoles
a
functional
intrinsic
apoptotic
cascade.
The
released
are
not
enclosed
membrane
can
replicate
in
In
summary,
our
data
argue
non-synchronous
way
late
Apoptosis-induction
important
other
pathways
most
likely
contribute.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: April 26, 2022
Abstract
Intracellular
bacteria
such
as
the
pathogen
Coxiella
burnetii
inject
effector
proteins
into
host
cell
that
promote
productive
infection.
One
common
strategy
of
effectors
is
to
suppress
immune
responses
enable
replication.
The
C.
type
IV
secretion
system
translocates
a
large
number
cells
collectively
intracellular
bacterial
replication,
but
individual
functions
most
these
are
poorly
understood.
In
this
study,
we
describe
effector,
CBU1314,
localizes
nucleus
and
inhibits
NF-κB-,
MAPK-,
I
IFN-dependent
gene
expression.
Mechanistically,
find
CBU1314
interacts
with
PAF1
complex
(PAF1C),
central
transcriptional
regulates
expression
inflammatory
genes
in
innate
cells.
Notably,
promotes
response
various
agonists
Moreover,
critical
for
restricting
Overall,
our
findings
uncover
PAF1C
target
reveal
new
insight
how
pathogens
subvert
cell-
intrinsic
defenses.
Significance
often
employ
secreted
modulate
cellular
processes
survive
intracellularly.
study
can
provide
valuable
microbial
pathogenesis
biology.
Here,
multiple
signaling
pathways
modulates
response.
This
regulator
transcription.
Furthermore,
show
necessary
maximal
downstream
receptors
restricts
replication
during
elucidates
function
evading
provides
role
cell-intrinsic
defense
against
pathogens.