Enterobacteriaceae

미생물학교실

권 형 주

-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

Enterobacteriaceae

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

- 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

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

Escherichia colio gastroenteritiso extraintestinal infections : urinary infections, meningitis, sepsis

o Pathogenesis and Immunity - Two general categories : Adhesins, Exotoxins

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)

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

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

2) Enteropathogenic E. coli (EPEC) • small intestine • fever• watery diarrhea• vomiting • nausea • person-to-person spread

• 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

destruction of surface microvilli

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

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•hemolytic-uremic syndrome (HUS) - hemolytic anemia

- thrombocytopenia (low platelets) - kidney failure

• Ingestion of fewer than 100 bacteria can produce disease

•Person-to-person spread

• Usually O157:H7

• 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

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

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

O Clinical diseases (Gastroenteritis)

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

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

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)

2) Septicemia

3) Enteric fever – Typhoid fever, paratyphoid fever

• S. Typhi, S. Paratyphi, S. Choleraesuis

Typhoid• enteric fever• severest salmonella disease• Salmonella typhi• epidemics

– third world– Europe

* historical

acute phase, gastroenteritis

gall bladder–shedding, weeks

septicemia- occurs 10-14 days– lasts 7 days

gastrointenteritis

Shigella

• S. flexneri, S. boydii, S. sonnei, S. dysenteriae– bacillary dysentery– shigellosis

•bloody feces• intestinal pain•pus

O Pathogenesis and Immunity

O Epidemiology

• 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

• Human are the only reservoir• Transmitted person-to-person

Shigellosis

• 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

O Clinical diseases

Yersinia• Y. pestis, Y. enterocolitica, Y.

pseudotuberculosis

Yersiniosis•transmission

– fecal contamination, domestic animals• Water, milk

– meat

• Diarrhea• fever• abdominal pain• antibiotic therapy recommended• occassional bacteremia

Klebsiella• K. pneuminiae, K.

oxytoca - lobar pneumonia• K. granulomatis - granuloma inguinale