1. Enterobacteriaceae
미생물학교실
권 형 주

2. Enterobacteriaceae The largest, most heterogeneous collection
Gram-negative rods
Ubiquitous
: Always associated with human disease
- Salomonella serotype Typhi(장티푸스균),
Shigella species (이질균),
Yersinia pestis (페스트균)
: Opportunistic infections
- Escherichia coli (대장균),
Klebsiella pneumoniae (폐렴막대균),
Proteus mirabilis

3. Physiology and Structure
Gram-negative rods
Enterobacterial common antigen
do not form spores
Facultative anaerobes
Simple nutrient requirements
(ferment glucose, reduce nitrate)
Catalase positive
Oxidase negative
(absence of cytochrome oxidase)
Few exception (text)
Ferment lactose (MacConkey agar)
: Escherichia, Klebsiella, Enterobacter, Citrobacter, Serratia
Not ferment lactose
: proteus, Salmonella, Shigella, Yersinia spp
- Resistance to bile salts : Shigella, Salmonella

4. Heat-stable LPS
: O polysaccharide – episemiologic classification of strains within a species
: Core polysaccharide
– Enterobacterial common antigen; Enterobacteriaceae classification
: Lipid A - endotoxin activity, virulence factor
Episemiologic (serological) classification of the Enterobacteriaceae
(장내세균의 혈청학적 분류)
: Somatic O polysaccharides
: Capsular K antigen
: Flagellar H proteins

5. Pathogenesis and Immunity
o Endotoxin : LPS (Lipid A)
o Capsule
: Hydrophilic capsular antigens – protect from phagocytosis
: interfere with the binding of antibodies
: poor immunogens
: poor activator of complement
o Antigenic phase variation
: capsular K, flagellar H antigens
o Type III secretion systems
: Common effector system for delivering their virulence factors
into targeted eukaryotic cells
o Sequestration of growth factors
: siderophores
: iron-chelating compounds – enterobactin, aerobactin
o Resistance to serum killing
: prevent the binding of complement components
o Antimicrobial resistance
: transferable plasmid

6. Escherichia coli o Pathogenesis and Immunity o gastroenteritis
o extraintestinal infections
: urinary infections, meningitis, sepsis
o Pathogenesis and Immunity
- Two general categories
: Adhesins, Exotoxins

7. 1) Enterotoxigenic E. coli (ETEC) 2) Enteropathogenic E. coli (EPEC)
O Epidemiology
Gastrointestinal tract
Opportunistic pathogens
Most common gram-negative rods isolated from patients with sepsis
Community-acquired infection > haopital-acquired infections
Developing country
Incidence of enterobacteriaceae associated with bacteremia
O Clinical diseases (Gastroenteritis)
1) Enterotoxigenic E. coli (ETEC)
2) Enteropathogenic E. coli (EPEC)
3) Enteroaggregative E. coli (EAEC)
4) Enterohemorrhagic E. coli (EHEC)
5) Enteroinvasive E. coli (EIEC)

8. 1) Enterotoxigenic E. coli (ETEC)
small intestine
diarrhea like cholera
milder
traveler’s diarrhea
Heat-labile toxin (LT-I, LT-II)
like cholera toxin (A subunit + 5 B subunits)
B subunits – GM1 gangliosides (epithelial cells) interaction
A subunit translocation
Adenyl cyclase activated (ADP ribosylation)
cyclic AMP
secretion water/ions, fluid loss
Heat stable toxin (STa)
Monomeric peptide
Guanylate cyclase activated
cyclic GMP
Hypersecretion of fluids

9. 2) Enteropathogenic E. coli (EPEC)
small intestine
fever
watery diarrhea
vomiting
nausea
person-to-person spread
destruction of surface microvilli
Bacterial attachment to epithelial cells
Formation of microcolonies
- Bundle forming pili (BFP) (plasmid-encoded)
- locus of enterocyte effacement (LEE) pathogenicity island
Destruction of host cell surface
Active secretion of proteins into host epithelial cells
- Type III secretion system
- Translocated intimin receptor (Tir), intimin
Polymerization of actin, accumulation of cytoskeletal elements
Loss of cell surface integrity
Cell death

10. 3) Enteroaggregative E. coli (EAEC)
small intestine
persistent watery diarrhea
vomiting
dehydration
low-grade fever
Autoagglutination
- AAFI (aggregative adherence fimbriae I), AAF/II, AAF/III
Formation of thick biofilms
Toxins
- EAST (enteroaggregative heat stable toxin)
- PET (plasmid encoded toxin)
Fluid secretion

11. 4) Enterohemorrhagic E. coli (EHEC)
large intestine
undercooked beef, meat, water, milk, fruit juices
watery diarrhea  bloody diarrhea (hemorrhagic colitis)
abdominal pain
vomiting
little or no fever
Usually O157:H7
hemolytic-uremic syndrome (HUS)
- hemolytic anemia
- thrombocytopenia (low platelets)
- kidney failure
Ingestion of fewer than 100 bacteria can produce disease
Person-to-person spread
Shiga toxin (Stx-1, Stx-2)
- Shigella dysenteriae
A subunit + 5 B subunits
B subunit – globotriaosylceramide (GB3)
(intestinal villus, renal endothelial cells)
A1 fragment – 28s rRNA binding
Cessation of protein synthesis

12. 5) Enteroinvasive E. coli (EIEC)
large intestine
watery diarrhea
vomiting
cramping
fever
dysentery
bloody stools
Pathogenic strains
- O124, O143, O164
Invade and destroy the colonic epithelium

13. 1) Urinary tract infection
O Clinical diseases (Extraintestinal infections)
1) Urinary tract infection
Adhesins – P pili, AAF/I, AAF/III, Dr
- bladder, upper urinary tract
hemolysin HlyA
- lyses erythrocytes
2) Neonatal meningitis
K1 capsular antigen
3) Septicemia

14. O Clinical diseases (Gastroenteritis)

15. Salmonella More than 2,500 antigenic "types” (serotypes)
genetically single species
S. enterica
(S. enterica, serovar. Typhi  S. Typhi)
disease category
S. enteritidis
many serotypes
S. choleraeuis
S. typhi

17. O Pathogenesis and Immunity
Attach to the mucose of the small intestine
Invade into the M (microfold) cells
Endocytic vacuole (replicate)
Pathogenicity island I (PAI I)
- Invasion proteins (Ssps)
- type III secretion system
Pathogenicity island II (PAI II)
- evade the host’s immune response
- Type III secretion system
O Epidemiology
Animal reservoir : animal-to-animal spread
Adapted to humans – S. Typhi, S. paratyphi
Ingestion of contaminated food products
Direct fecal-oral spread
Poultry, eggs, dairy products

18. S. enteritidis 1) Gastroenteritis the common salmonella infection
O Clinical diseases
1) Gastroenteritis
The most common form of salmonellosis
S. enteritidis
the common salmonella infection
poultry, eggs
no human reservoir
Gastroenteritis
nausea
vomiting
non-bloody stool (nonbloody diarrhea)
self-limiting (2 - 5 days)

19. 2) Septicemia
S. Typhi, S. Paratyphi, S. Choleraesuis
3) Enteric fever – Typhoid fever, paratyphoid fever
Typhoid
enteric fever
severest salmonella disease
Salmonella typhi
epidemics
third world
Europe
historical
septicemia
- occurs days
lasts 7 days
gall bladder
shedding, weeks
acute phase, gastroenteritis
gastrointenteritis

20. Shigella S. flexneri, S. boydii, S. sonnei, S. dysenteriae
bacillary dysentery
shigellosis
bloody feces
intestinal pain
pus

22. O Pathogenesis and Immunity
Invading and replicating in cells lining the colon
Cell-to-cell spread
Type II secretion – IpaA, IpaB, IpaC, IpaD  epithelial cells, macrophages
Replicate in the host cell cytoplasm
Shiga toxin
Enterotoxic (damage to intestinal epithelium)
Cytotoxic
damage to glomerular endothelial cells  renal failure (HUS)
A subunit + 5 B subunits - GB3
inhibits protein synthesis
- lysing 28S rRNA
O Epidemiology
Human are the only reservoir
Transmitted person-to-person

23. Shigellosis O Clinical diseases
Andominal cramps, diarrhea, fever, bloody stools
Human only "reservoir"
mostly young children
fecal to oral contact
children to adults
transmitted by adult food handlers
unwashed hands

24. Yersinia
Y. pestis, Y. enterocolitica, Y. pseudotuberculosis

25. Yersiniosis transmission fecal contamination, domestic animals
Water, milk
meat
Diarrhea
fever
abdominal pain
antibiotic therapy recommended
occassional bacteremia

26. Klebsiella K. pneuminiae, K. oxytoca - lobar pneumonia K. granulomatis
- granuloma inguinale