SHIGELLA

1
SHIGELLA
2

• Genus Shigella belongs to Enterobacteriaceae
  family
• Shigella has been traditionally been grouped with
  Salmonella and Yersinia because these 3 genera
  are invasive organisms that do not ferment
  lactose.
• However, recent taxonomic studies that have
  focused on DNA homology have shown that Shigella
  is closely related to Escherichia, and some
  researchers believe that it is a subspecies of
  Escherichia coli.

3
General features

• Four species (groups) of Shigella has been
  identified
• Shigella dysenteriae (group A), (12 serotypes)
• Shigella flexneri (group B), (6 serotypes)
• Shigella boydii (group C), (18 serotypes)
• Shigella sonnei (group D). (1 serotype).

4

• Members of the genus Shigella are the principal
  agents of bacillary dysentery.
• This disease differs from profuse watery
  diarrhea, as is commonly seen in choleraic
  diarrhea or in enterotoxigenic Escherichia coli
  diarrhea, in that the dysenteric stool is scant
  and contains blood, mucus, and inflammatory
  cells.

5
(No Transcript)
6
Epidemiology

• Shigella is one of the most infectious of
  bacteria and ingestion of as few as 100-200
  organisms will cause disease.
• Most individuals are infected with shigellae when
  they ingest food or water contaminated with human
  fecal material.
• Shigellae can survive up to 30 days in milk,
  eggs, cheese or shrimps.

7

• Spread is always from a human resource and
  generally involves one of the five fs
• food,
• fingers,
• feces,
• flies or
• fomites.
• This is in contrast to salmonellae, which are
  often spread to humans from infected animals.

8

• Shigellosis is primarily a pediatric disease
• 70 of all infections occur in children younger
  than 15 yars
• Dysentery outbreaks are usually associated with
  closed populations, such as
• families,
• cruise ships,
• mental hospitals,
• children in day-care facilities, and
• prisoners.

9
PATHOGENESIS

• Bacterial products involved in virulence
• Shigella cause disease by invading, replicating
  in cells linning the colonic mucosa, and cell to
  cell spread.
• The ability of shigellae to invade host cells
  depends on the presence of a 220 kb plasmid that
  encodes for a set of 4 proteins known as invasion
  plasmids antigens (IpaA, IpaB, IpaC, IpaD).
• One of these antigens, IpaD, is believed to be an
  adhesin that allows the bacterium to be
  phagocytosed.
• The host cell receptor for IpaD is not known, but
  it is expressed only on the basolateral pole of
  enterocytes.

10

• Once the shigella is inside the host phagosome, a
  cell-associated hemolysin lyse the phagosome, and
  the bacterium multiplies within the cell
  cytoplasm.

11

• Within 2 hours of entry, the shigella is coated
  with gelatinized actin.
• This coat is soon converted to a tail of
  polymerized actin that streams away from the
  bacterium.
• Actin polymerization is caused by a 120 kD outer
  membrane protein.
• This polymerization allows the shigella to move
  directly from cell to cell.

12

• Shigella dysenteriae produces Shiga neurotoxin.
• This toxin is identical to verotoxin 1 produced
  by enterohemorrhagic strains of E. coli and it
  has one A subunit and five B subunits.
• The B subunits bind to a host cell glycolipid
  (Gb3) and facilitate transfer of the A subunit
  into the cell. The A subunit disrupts protein
  synthesis.
• The primary manifestation of toxin activity is
  damage to the intestinal epithelium.
• In some cases, Shiga toxin can mediate damage to
  the glomerular endothelial cells, resulting in
  renal failure.

13

• Shiga toxin production is not need to kill host
  colonic epithelial cells in fact invasion seems
  to be the critical event in cell death and kills
  host cells faster than does Shiga toxin.
• Nevertheless, shigellae that produce Shiga toxin
  cause more severe disease, possibly because the
  toxin damages the capillaries of the lamina
  propria of the colonic villi, causing ischemia
  and hemorrhagic colitis.

14
The Shigella infection cycle

• Shigellae transiently infect the small intestine
  during the first few days of disease, and
  dysentery occurs when the colon is infected.
• Invasion of the colon is probably initiated
  through colonic lymphoid follicles that are rich
  in M (microfold) cells and are analogous to
  Peyers patches found in small intestine.
• These cells (M cells) typically transport foreign
  antigens to the underlying macrophages for
  clearance.

15

• A proposed model for invasion of epithelial
  cells of the colon.
• 1) The Shigella first cross the mucosa by
  passing through specialized cells called M cells.
  
• The M cell passes the Shigella on to a macrophage
  from which it subsequently escapes - possibly by
  inducing apoptosis, a programmed cell suicide.

16

• 2) The Shigella then uses its invasins to enter
  the mucosal epithelial cells from underneath.
• The invasins cause actin polymer rearrangements
  in the cell's cytoskeleton resulting in the
  bacterium being engulfed and placed in an
  endocytic vesicle in a manner similar to
  phagocytic cells.
• Once inside, the Shigella escape from the vacuole
  into the cytoplasm and multiply.

17

• 3) The Shigella are able to move through the host
  cell and spread to adjacent host cells by a
  unique process called actin-based motility.
• In this process, actin filaments polymerize at
  one end of the bacterium, producing comet-like
  tails that propel the Shigella through the
  cytoplasm of the host cell.

18

• 4) When they reach the boundary of that cell, the
  actin filaments push the Shigella across that
  membrane and into the adjacent cell.

19
(No Transcript)
20

• Some shigellae subsequently invade the connective
  tissue (the lamina propria), elicit an
  inflammatory response, and cause ulceration at
  the invasion site.
• The inflammatory response involves PMNs and
  fibrin pseudomembrane typically forms over the
  ulcer.

21

• Shiga toxin may exacerbate the inflammation by
  causing ischemia and hemorrhage.
• Shiga toxin that enters the circulation may also
  cause hemolytic-uremic syndrome.
• Unlike salmonellae, shigellae are restricted to
  the mucosa and submucosa and rarely cause
  bacteriemia or sepsis.

22
CLINICAL DISEASE

• Two to three days after exposure to shigellae,
  the symptoms of shigellosis begin.
• There is a sudden onset of
• fever,
• abdominal cramping and tenderness, and
• diarrhea.

23

• During the first 2-3 days, fluid loss may be
  extensive and may endanger the lives of children
  and others that tolerate fluid and electrolyte
  loss poorly.
• However, the cardinal feature of shigellosis is
  lower abdominal cramps and tenesmus,with abundant
  pus and blood in the stool.
• The onset of tenesmus (straining at stool) is
  usually accompanied by decrease in the number and
  volume of stools

24

• Sigmoidscopy reveals that the mucosa is hyperemic
  and hemorrhagic and demonstrates the presence of
  ulceration covered with fibrin pseudomembrane.
• The finding of mucus, PMNs, and blood in the
  stool is hallmark of dysentery and indicates that
  the bowel wall has been invaded.

25

• To identify the causative agent, stool samples
  can be cultured.
• The best sample for culture, however, consists of
  a rectal swab of an ulcer and is obtained during
  sygmoidoscopy.
• Dysentery due to Shigella must be differentiated
  from dysenterylike diseases caused by
  enteroinvasive E. coli, Campylobacter jejuni, and
  the parasite Entamoeba histolytica.