Hybrid and potentially pathogenic Escherichia coli strains - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 330

in adherence and invasion, occurs in a strain defective in the NlpI lipoprotein
( Barnich et al., 2004 ). The flagellar transcriptional regulator FlhD2C2 and
the sigma factor FliA are required for the expression of type I pili, while the
effect of FliA is partially mediated through YhjH, a phosphodiesterase involved
in degradation of dimeric cGMP ( Claret et al., 2007 ). While high osmolarity
induces an increase in the ability of AIEC to interact with human cells and
correlates with an increase in OmpC porin expression, an ompC null mutant
expresses neither flagella nor type I pilli, and this effect is mediated by the RNA
polymerase σ E factor ( Rolhion et al., 2007 ). In contrast, down-regulation of the
histone-like protein Fis, occurring during AIEC infection of IECs, produces a
repression of flagella expression and leads to the preferential ON status of the
fim switch ( Miquel et al., 2010a ).
A Caenorhabditis elegans -based model for in vivo AIEC infection was devel-
oped and used to test whether Hfq RNA chaperone, which is involved in post-
transcriptional regulation by small non-coding RNA, is required for full virulence.
The hfq mutant is non-motile, less invasive and highly sensitive to chemical stress,
indicating that post-transcriptional ribo-regulation mediates AIEC adaptation to
this environmental niche ( Simonsen et al., 2011 ). The transcription of the HtrA
stress protein and the DsbA oxidoreductase, required for intramacrophage repli-
cation, are highly up-regulated in intramacrophagic bacteria and/or macrophage-
mimicking stress culture conditions, but their activation is independent of the
CpxRA two-component regulatory system ( Bringer et al., 2005, 2007 ), which
regulates HtrA and DsbA expression in non-pathogenic E. coli strains.
Avoidance of host responses
AIEC is able to translocate across in vitro cultured M cells monolayers ( Chas-
saing et al., 2011 ). Enteric pathogens crossing the follicle-associated epithelia
need to survive phagocytosis and bacterial killing by resident and recruited mac-
rophages at the dome of the lymphoid follicle. Pathogenic bacteria counteract
macrophage killing after phagocytosis, either by escaping phagosomes and induc-
ing cell death, or by resisting the antimicrobial environment of the phagosome,
which includes inhibition of its fusion with lysosomes. AIEC is able to survive
and replicate within macrophages, in which they reside in a large vacuole without
inducing cell death ( Glasser et al., 2001 ). In contrast to other pathogens, AIEC-
containing phagosomes traffic through the endocytic pathway and mature into
active phagolysosomes where bacteria are exposed to low pH and the proteolytic
activity of cathepsin D ( Bringer et al., 2006 ). AIEC has developed mechanisms
to resist phagosome stress conditions and mutations in htrA or dsbA increase the
sensibility of the bacteria to acid and nutrient-limiting growth conditions and
oxidative stress caused by hydrogen peroxide, which correlates with a defect in
intramacrophagic replication ( Bringer et al., 2005, 2007 ).
Putative genetic determinants predisposing humans to CD include poly-
morphisms of the gene encoding the intracellular receptor NOD2 / CARD15