1. Enterobacteriaceae Chapter 31

2. Introduction  “Enteric Bacteria”  Gram-negative rods  Ubiquitous  Cause 30%-35% of all septicemias, more than 70% of UTIs, and many intestinal infections  Pathogens: Normal flora – opportunistic infections Animal reservoirs Human carriers  Box 31-1

3. BOX 31-1. Common Medically Important Enterobacteriaceae  Citrobacter freundii, Citrobacter koseri  Enterobacter aerogenes, Enterobacter cloacae  Escherichia coli  Klebsiella pneumoniae, Klebsiella oxytoca  Morganella morganii  Proteus mirabilis, Proteus vulgaris  Salmonella enterica  Serratia marcescens  Shigella sonnei, Shigella flexneri  Yersinia pestis, Yersinia enterocolitica, Yersinia pseudotuberculosis

4. Physiology and Structure  Facultative anaerobes  Ferment glucose, are catalase positive, and oxidase negative  Lactose fermenting strains (e.g. Escherichia, Klebsiella, Enterobacter)  Non-lactose fermenting (e.g. Salmonella, Shigella, and Yersinia)

5. Differentiating Similar Strains Antigen detection  O polysaccharides Part of LPS  Capsular K  Flagellar H proteins  E. coli O157:H7

6. Pathogenesis and Immunity Common virulence factors  Endotoxin Lipid A portion of LPS causes many of the systemic manifestations of infection  Capsule Interferes with antibody binding Capsular antigens are hydrophilic (phagocytic cell surface is hydrophobic) Poor antigenicity  Antigenic phase variation Capsular K and flagellar H antigens are under genetic control Can be expressed or not expressed

7. Pathogenesis and Immunity  Sequestration of growth factors Iron: Bacteria produce competitive siderophores or iron-chelating compounds, hemolysins

8. Escherichia coli Pathogenesis (Box 31-3)  Adhesins: Essential for colonization Prevents the organism from being flushed out of the urinary or gastrointestinal tract  Exotoxins Specific target tissue Result in altered cell function or cell death

9. Epidemiology and Clinical Diseases  Many infections are endogenous (septicemia and UTI’s)  Septicemia-originate from UT or GI infections leading to intraabdominal infection  Neonatal meningitis, Intraabdominal infections  UTIs-originate in the colon -> contaminate urethra -> ascend into the bladder Production of adhesins ~80% of all community-acquired UTIs  Gastroenteritis-caused by five major groups May include: watery diarrhea, abdominal cramps, fever, and vomiting (Table 31-1)

10. Gastroenteritis (ETEC)  Estimated 80,000 cases in US travelers annually (650 million worldwide)  In small intestine; watery diarrhea, cramps, vomiting, fever  Occurs in developing countries usually in children or travelers (traveler’s diarrhea)  1-2 day incubation, 3-4 duration  Infectious dose is high so person to person spread does not occur  Two classes of enterotoxins: heat-labile (LT-I, LT-II) and heat-stable (STa, STb) LT-I increases secretion of chloride and inhibits absorption of sodium and chloride (the same as cholera toxin) STa causes a hypersecretion of fluids  Both contributing to watery diarrhea  Disease similar to cholera, but milder

11. Gastroenteritis (ETEC) Imodium mode of action: http://en.wikipedia.org/wiki /Loperamide

12. Gastroenteritis (EHEC)  73,000 cases with 60 deaths annually  In large intestine; vomiting, abdominal cramps, fever  Severity ranges from diarrhea to hemorrhagic colitis (bacterial dysentery)  3-4 day incubation, 4-10 day duration  Infectious dose is less than 100 bacteria, O157:H7 serotype is the most common  Read text page 329  Shiga toxins (Stx-1, Stx-2) Bind to 28S rRNA and disrupt protein synthesis Tissue destruction leads to the symptoms (bloody diarrhea)

13. Gastroenteritis (EHEC)  Spinach Outbreak Information  http://www.cdc.gov/mmwr/preview/ mmwrhtml/mm55d926a1.htm http://www.cdc.gov/mmwr/preview/ mmwrhtml/mm55d926a1.htm  http://www.cfsan.fda.gov/~dms/spin acqa.html#howmany http://www.cfsan.fda.gov/~dms/spin acqa.html#howmany

14. Salmonella Characteristics  Similar to E. coli except no lactose fermentation  Historically there have been many different species (~2000) All are really one species: Salmonella enterica

15. Salmonella Virulence factors  Box 31-2 and 31-5  Some bacteria can survive stomach acid  Able to enter M cells (peyer’s patches)  Cause cell death and spread to surrounding cells.  Figure

17. Salmonella Epidemiology Colonize virtually all animal species

18. Salmonella Diseases (Gastroenteritis)  Most common form of disease 40,000 cases in the US in 2004  Mostly spread by eating contaminated food (Poultry, eggs, dairy products)  Can be fecal-oral in children  Infectious dose 10 6 to 10 8  Symptoms 6-48hrs after consumption nausea, vomiting, non-bloody diarrhea, fever, abdominal cramps  Usually ends without intervention in a week or less

19. Salmonella Diseases (Typhoid Fever)  Typhoid Fever  Human reservoir (person-to-person spread)  Pass through intestinal lining and engulfed by phagocytes Replicate in liver, spleen, bone marrow  Cause fever, myalgia, gastroenteritis  Asymptomatic colonization (1-5% patients) Story Time - “Typhoid Mary”

20. Salmonella Treatment  Preventative - safe food preparation Antibiotics not recommended for enteritis  Typhoid Fever - antibiotics

21. Shigella  Characteristics  Gram - facultative anaerobe, rod  DNA hybridization reveals they’re actually biogroups of E. coli.  Don’t ferment lactose  Intracellular pathogen

22. Shigella Virulence Factors  Adhere to, invade, and replicate in M cells (Peyer ’ s Patches).  Spread to macrophages and cause lysis of phagocytic vacuole They then replicate in the cytoplasm  Cause apoptosis, and release of IL-1β which attract polymorphonulear leukocytes which destroy intestinal tissue.  Shiga toxin — disrupts protein synthesis Remember E. coli O157:H7

23. Shigella Epidemiology  Estimated 450,000 cases in U.S. (2003) 150 million world wide  Spread by fecal oral route (yummy).  Primarily a pediatric disease 70% occur in children 15 and under.  Highest risk in daycares, nurseries, custodial institutions  Low infectious dosage (~200 cells)

24. Shigellosis  Symptoms appear 1-3 days after ingestion  Begin with watery diarrhea.  Progress to abdominal cramps and pus in bloody stool.  Usually clears up on its own Antibiotics are given to reduce the chance of spread  Small percentage of asymptomatic colonization

25. Yersinia Species  Y. pestis – causes the plague Highly virulent pathogen causing a systemic disease  Y. enterocolitica - causes enterocolitis

26. Yersinia Virulence Factors  Found on plasmids  Capsule  Antiphagocytic proteins  Proteins which cause apoptosis in macrophages  Proteases which inactivate compliment proteins  Fibrinases which break down blood clots

27. Yersinia Epidemiology  Humans are accidental hosts Most infections in other animals are fatal (not normal flora)  Y. enterocolitica Reservoir rabbits, rodents, pigs, livestock Primarily in colder climates 90% infections associated with ingestion of contaminated meat, milk, water  Mostly in children

28. Yersinia entercolitica  Symptoms include: diarrhea, abdominal pain, fever Can mimic acute appendicitis  Usually lasts 1 to 2 weeks  Because of growth at low temperature (4°C) can spread in blood products

29. Yersinia pestis Epidemiology Sylvatic Plague  Reservoir is small mammals, livestock etc.  Too widespread for animal control  Can spread by eating contaminated food

30. Yersinia Pestis Epidemiology Urban plague  Reservoir is rats, transmitted by fleas  Rare due to good hygiene, and rat control  Three great pandemics.

31. Plague History  Egypt 541 AD. lasted 200yrs Spread to most of the “old world” Killed a majority of the population  1320s, over 5 year period 25 million died in Europe (30-40% of population)  China 1860s spread world wide  About 10 cases in the U.S. per year Sylvatic plague

32. Yersinia Diseases Bubonic Plague incubation of no more than 7 days cause bubos (swelling of lymph nodes) in groin and armpit 75% mortality in untreated cases

33. Yersinia Diseases Pneumonic Plague short (2-3 day) incubation fever, malaise, pulmonary signs highly infectious 90% mortality for untreated patients

34. Yersinia Treatment  Y. pestis–streptomycin, tetracyclines, chloroamphenicol  Enteric infections usually clear on there own  Urban plague is controlled by reducing the rodent population