Listeria monocytogenes is a human
intracellular pathogen able to colonize host tissues after
ingestion of
contaminated food, causing severe invasive
infections. In order to
gain a better understanding of the nature of host-pathogen interactions, we studied the
L. monocytogenes genome expression during
mouse infection. In the
spleen of infected
mice, approximately 20% of the
Listeria genome is differentially expressed, essentially through
gene activation, as compared to exponential growth in rich broth medium. Data presented here show that, during
infection,
Listeria is in an active multiplication phase, as revealed by the high
expression of genes involved in replication,
cell division and multiplication. In vivo
bacterial growth requires increased
expression of genes involved in adaptation of the
bacterial metabolism and
stress responses, in particular to
oxidative stress.
Listeria interaction with its host induces
cell wall metabolism and surface expression of
virulence factors. During
infection,
L. monocytogenes also activates subversion mechanisms of host defenses, including resistance to
cationic peptides,
peptidoglycan modifications and release of muramyl
peptides. We show that the in vivo differential expression of the
Listeria genome is coordinated by a complex regulatory network, with a central role for the PrfA-SigB interplay. In particular,
L. monocytogenes up regulates in vivo the two major
virulence regulators, PrfA and VirR, and their downstream effectors. Mutagenesis of in vivo induced genes allowed the identification of novel
L. monocytogenes virulence factors, including an LPXTG surface protein, suggesting a role for
S-layer glycoproteins and for
cadmium efflux system in
Listeria virulence.
