Biology Reference
In-Depth Information
Chromosomally encoded
In contrast to the genes of the virulence plasmid that are responsible for invasion
of mammalian tissues, most of the chromosomal loci associated with
Shigella
virulence are involved in regulation or survival within the host. Mutations that
alter O-antigen and LPS core synthesis or assembly lead to a 'rough' phenotype
and render
Shigella
avirulent. As mentioned earlier, synthesis of a complete
LPS, which is crucial for correct unipolar localization of IcsA, requires chro-
mosomal loci such as
rfa
and
rfb
. In the case of
S. sonnei
and
S. dysenteriae
1,
plasmid-borne genes encode the enzymes necessary for synthesis of the LPS
O-side chain (
Brahmbhatt et al., 1992
). LPS has also been implicated as an
important indirect chemoattractant since the molecule induces IL-8 expression
in epithelial cells to recruit PMNs to the intestinal lumen thereby promoting tis-
sue injury and amplification of the
Shigella
infectious cycle.
The
stx
locus encodes Shiga toxin in
S. dysenteriae
1. Shiga toxin inhibits
protein synthesis by cleaving the N-glycosidic bond at adenine 4324 in the 28S
ribosomal RNA of mammalian cells (
Melton-Celsa et al., 2012
). Animal studies
suggest that Shiga toxin is responsible for the more severe vascular damage in
the colonic tissue observed during
S. dysenteriae
1 infection. Shiga toxin is also
produced, at even higher levels, by enterohemorrhagic
E. coli
and is associated
with glomerular damage and kidney failure. The resulting hemolytic uremic
syndrome (HUS), linked to Shiga toxin-producing pathogens, may lead to death
(
Butler, 2012
). There is no evidence for the presence of an
stx
allele in the other
species of
Shigella
nor in EIEC. Thus production of Shiga toxin may account
for the generally more severe infections caused by
S. dysenteriae
1.
Two pathogenicity islands have been identified in the chromosome of
S. flexneri
and a third has been described in
S. boydii
. The
Shigella
pathogenic-
ity island 1 (SHI-1), which is only present in
S. flexneri
2a, contains the
set
gene
that encodes a second enterotoxin, ShET-1 (
Fasano et al., 1995
;
Rajakumar et al.,
1997
). The
set
gene is contained within the open reading frame of another gene,
she
, which encodes a protein with putative hemagglutinin and mucinase activ-
ity. The SHI-2 pathogenicity island is broadly distributed in the shigellae and
contains the
iuc
locus, which encodes the genes for synthesis of aerobactin and
its outer membrane receptor (
Moss et al., 1999
;
Vokes et al., 1999
). Aerobactin
is a hydroxamate siderophore that
S. flexneri
uses to scavenge iron. When the
iuc
locus is inactivated in
S. flexneri
, the aerobactin deficient mutants retain their
capacity to invade host cells but are altered in virulence as measured in animal
models. These results suggest that aerobactin synthesis is important for bacterial
growth within the mammalian host (
Nassif et al., 1987
). SHI-3 of
S. boydii
con-
tains an aerobactin locus that is 97% identical at the DNA level to that of SHI-2
(
Purdy and Payne, 2001
). This island shares other genes found on SHI-2 but its
location on the genome is different. SHI-2 is inserted downstream of
selC
while
SHI-3 is located between
lysU
and
pheU
. Although EIEC synthesize aerobactin,
the
iuc
genes are not contained on a SHI-2-like pathogenicity island near
selC
.
The chromosomal location of the
iuc
genes in EIEC remains to be determined.
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