| SPI-3 (17-kb pathogenicity
island located at 82 min, just behind the selC tRNA
locus of Salmonella) |
in the mgtCB operon, the gene mgtC is specific for Salmonella.
mgtB which is a Mg2+ transporting ATPase. Another
Mg2+ transporter coded by SPI-3 is mgtA. SPI-3. It also harbors the marT-fidL operon, encoding
MarT transcriptional regulator and a hypothetical protein FidL |
in the mgtCB operon, the gene mgtC is specific for Salmonella, facilitates intramacrophage survival, growth in low Mg2+ media, and survival in acidic environments of endosomes resulting
from SPI-1-mediated invasion. MisL, coded by SPI-3, is an extracellular
matrix adhesin involved in intestinal colonization |
the region adjacent to the selC tRNA region hosts the maximum amount of variations
between S. Typhi and S. Typhimurium
along with some pseudogenes like STY4024 (cigR),
STY4027 (marT), STY4030 (misL),
STY4034, STY4035, and STY4037. a few more pseudogenes are also noted
in other regions of SPI-3 like STY4012, STY4007, and STY4003. in brief,
MisL, its regulator MarT, and an unknown putative transcriptional
regulator (STY4012) are inactivated in S. Typhi.
expression of S. Typhimurium marT-fidL in S. Typhi negatively affected the survival of
the bacterium inside macrophage cells but not epithelial cells |
(291−295) |
| SPI-4
(24 kb fragment located
next to a potential tRNA-like gene at centisome 92) |
SPI-4 encodes a type 1 secretion
system (siiCDF), which encodes the almost 600 kDa
protein (encoded by SiiE) |
SiiE is a nonfimbrial adhesin
protein, 600 kDa in size, containing 53 repeats of Ig domains. SiiE
is secreted into the culture medium and mediates contact-dependent
adhesion to the epithelial cell surface |
SPI-4 has role in the intracellular
uptake and survival in macrophages for S. Typhi.
SiiE is coded by only one ORF in S. Typhimurium (STM4261),
unlike in S. Typhi, where it is segmented into two
ORFs in S. Typhi (STY4458 and STY4459) due to the
presence of a stop codon. this implies that siiE is
a pseudogene in S. Typhi that correlates with the
loss of function of adhesin responsible for intestinal colonization
by S. Typhimurium |
(237, 296, 297) |
| SPI-5 (approximately 7.6
kb long and has been found next to serT tRNA) |
encodes the effector proteins
for both the T3SS system of SPI-1 and SPI-2 |
SopB translocated
by SPI-1
T3SS helps in membrane ruffling and invasion. PipA contributes in
the development of systemic infection. PipB translocated by SPI-2-encoded
T3SS facilitates accumulation of lipid rafts and helps in intramacrophage
survival |
no difference
has been observed
between the two serovars apart from an additional ORF (STY114) that
putatively encodes a transposase in S. Typhi |
(117, 298, 299) |
| SPI-6
(located next to aspV tRNA gene at centisome 47 and
it extends for 47 kb
and 59 kb in both S. Typhi and S. Typhimurium) |
SPI-6
has the saf gene and the pagN gene |
the saf gene codes for fimbriae and the pagN gene codes
for the invasion protein in both the serovars |
a fragment 10 kb in size
is present downstream of the saf operon only in S. Typhi, which includes putative transposase remnants (STY0343
and STY0344, both of which are pseudogenes), the fimbrial operon tcfABCD, and genes tinR (STY0349) and tioA (STY0350). although the T6SS gene cluster is intact
in S. Typhi, the protein complex is thought to be
nonfunctional due to the presence of a pseudogene form of SciI (VipB
homologue). Wang et al. have disproved this assumption and have identified
the genes sciA, sciG, sciS, and vrgS as important for T6SS function |
(299, 300) |
| SPI-7 (largest SPI, 133
kb, located between two partially duplicated copies of the tRNA-pheU gene and contains about 150 genes) |
encodes the capsular polysaccharides
or the Vi antigen. it contains the pil gene cluster
along with some of the genes of the conjugative plasmid like tra and sam
|
the pil gene cluster that is responsible
for coding many virulence factors
along with the SopE prophage (ST44) that encodes the SPI-1 effector
SopE |
the Vi capsule
also acts
to inhibit flagellin expression, causes limited recognition of Salmonella by NAIP, and helps to reduce levels of pyroptosis
and IL-1β secretion of macrophages. Along with this, Vi has
been reported to bind to cell surface, thus dampening the inflammation
caused by MAPK signaling or IL-8 production |
(301−303) |
| SPI-8
(6.8 kb and has been
next to pheV tRNA gene that is found next to SPI-13) |
|
|
the exact function of SPI-8
is yet to be elucidated but it is known to code for putative virulence
factors |
(120, 304) |
| SPI-9 |
encodes for virulence factors
of the type I secretion system and encodes RTX-like protein. It shares
a 40% nucleotide homology to siiCDEF genes from SPI-4 |
|
arranged in an
operon whose
promoter was upregulated in low pH and high osmolarity conditions
in a RpoS-dependent fashion. All the proteins encoded by this pathogenicity
island localize in the membrane faction, supporting their putative
role as T1SS. SPI-9 contributed to the adherence of S. Typhi to epithelial cells under high osmolarity or low pH or in
situation mimicking conditions of the small intestine |
(80, 298, 305) |
| SPI-10 (32.8 kb, next to leuX tRNA gene at centisome 93) |
In S. Typhimurium,
it is substituted by a 20 kb uncharacterized island without any SPI
annotation that comprises functionally unrelated genes sharing little
homology to sequences from the genomic database |
there is possible relationship
of this sequence with DNA repair, deletion of this island in S. Typhimurium 14028 attenuated the virulence of the strain |
a full P4-related phage
named ST46 that harbors prpZ as cargo genes responsible
for encoding the Ser-Thr protein involved
in S. Typhi survival in macrophages. many other pseudogenes
are also found in S. Typhi, namely, STY4835 (IS1230), STY4836 (sefA), STY4839 (sefD), STY4841 (sefR), STY4845 (a thiol–disulfide
interchange protein), and STY4848 (putative transposase). the homologous
ORFs STY4842–4846 of S. Typhi includes the srgA gene. The srgA gene encodes a functional
disulfide oxidoreductase in S. Typhimurium unlike
that in S. Typhi, where it is a pseudogene (STY4845).
it contributes to virulence factors that lead to the formation of
Sef fimbriae, a phenomenon restricted to S. Typhi
and S. Enteritidis. The role of cryptic bacteriophage
is yet to be elucidated |
(304, 306, 307) |
| SPI-11
(6.7 kb in S. Typhimurium and 10 kb in S. Typhi) |
|
|
S. Typhi
lacks the putative envelope lipoprotein envF, but
it retains six additional ORFs (STY1884–1891), including the
typhoid toxin CdtB. the CdtB toxin is elaborated in the section Interaction of Salmonella Typhi with
Phagocytes
|
(308) |
| SPI-12 (is located next
to proL tRNA centisome 48, 6.3 kb long in S. Typhi) |
|
SPI-12 is responsible
for
causing systemic infection in mice for S. Typhimurium
14028 |
in S. Typhi,
three ORFs are pseudogenes, viz., STY2466a, STY2468, and STY2469.
Only the sspH2 gene is functional in this island |
(146, 309) |
| SPI-13 (next to the pheV tRNA gene at centisome 67 in S. Typhimurium
and S. Typhi.; there is an 8 kb fragment different
in the serovars, which corresponds to SPI-8 in S. Typhi) |
In S. Typhimurium,
the ORFs STM3117–3123 code for virulence-associated genes |
the genes are involved in
intracellular replication in murine macrophages and contribute to
systemic infection of mice |
S. Typhi
SPI-8 harbors two bacteriocin immunity proteins (STY3281 and STY3283)
and four pseudogenes. The virulence properties of SPI-8 are unknown.
The conserved 17 kb in SPI-13 has not been found to contribute to
virulence |
(6, 310, 311) |
| SPI-14 |
|
the function of this SPI
has yet to be understood |
although these are found
in S. Enteritidis and S. Typhimurium,
they are absent from S. Typhi and S. Paratyphi A |
(304) |
| SPI-15 (6.5 kb island that
is present near the glyU tRNA gene in S. Typhi) |
|
absent in S. Typhimurium |
constitutes
five islands
encoding hypothetical proteins, which have been identified by bioinformatic
analysis |
(312) |
| SPI-16 (4.5 kb fragment
located next to argU tRNA) |
five ORFs in S. Typhimurium |
|
seven ORFs in S. Typhi. Four of
these genes are pseudogenes in S. Typhi. the three
remaining ORFs in S. Typhi have
a high level of similarity with P22 phage involved in seroconversion.
they are suggested to cause O-antigen glycosylation and cell surface
variation. |
(312, 313) |
| SPI-17 (inserted next to
an argW tRNA site) |
this pathogenicity island
contains seroconversion genes homologous to P22 phage |
it showed a high similarity
to genes of SPI-16, including a putative lipopolysaccharide modification
acyltransferase |
most
of these genes are
pseudogenes in S. Typhi |
(312) |
| SPI-18 |
This genomic island is missing
in S. Typhimurium |
|
codes for two putative genes.
One of these is hlyE, encoding a hemolysin related
to the Escherichia coli K12 HlyE hemolysin. Fuentes
et al. have shown that S. Typhi hlyE mutants are impaired in their capability to invade human epithelial
cells in vitro, and its heterologous expression in S. Typhimurium has been seen to improve the colonization of deep organs
in mice. additionally, a secreted 27 kDa invasin, coded by taiA (STY1499), increases bacterial uptake by human macrophages |
(304, 314, 315) |
