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Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.
[typhoid]
Vaccination
represents
an
important
instrument
to
control
typhoid
fever
in
humans
and
protects
mice
from
lethal
infection
with
mouse
pathogenic
serovars
of
Salmonella
species
.
Mixed
infections
with
tagged
Salmonella
can
be
used
in
combination
with
probabilistic
models
to
describe
the
dynamics
of
the
infection
process
.
Here
we
used
mixed
oral
infections
with
tagged
Salmonella
strains
to
identify
bottlenecks
in
the
infection
process
in
naïve
and
vaccinated
mice
.
We
established
a
next
generation
sequencing
based
method
to
characterize
the
composition
of
tagged
Salmonella
strains
which
offers
a
fast
and
reliable
method
to
characterise
the
composition
of
genome-tagged
Salmonella
strains
.
We
show
that
initial
colonization
of
Salmonella
was
distinguished
by
a
non-
Darwinian
selection
of
few
bacteria
setting
up
the
infection
independently
in
gut
associated
lymphoid
tissue
and
systemic
compartments
.
Colonization
of
Peyer
's
patches
fuels
the
sustained
spread
of
bacteria
into
mesenteric
lymph
nodes
via
dendritic
cells
.
In
contrast
,
infection
of
liver
and
spleen
originated
from
an
independent
pool
of
bacteria
.
Vaccination
only
moderately
reduced
invasion
of
Peyer
's
patches
but
potently
uncoupled
bacterial
populations
present
in
different
systemic
compartments
.
Our
data
indicate
that
vaccination
differentially
skews
the
capacity
of
Salmonella
to
colonize
systemic
and
gut
immune
compartments
and
provide
a
framework
for
the
further
dissection
of
infection
dynamics
.
