Enterobacteriaceae

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

7. 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. 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. 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 10-14 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. O Clinical diseases 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

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