Enterobacteriaceae 미생물학교실 권 형 주

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

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 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

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

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)

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 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

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 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

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

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

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

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)

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 10-14 days lasts 7 days gall bladder shedding, weeks acute phase, gastroenteritis gastrointenteritis

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

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

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

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