1. Microbiology of the Gastrointestinal Tract

2. Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

3. Food Poisoning Main bug details gram stain, morphology pathogenic features food of choice Clinical setting Diagnosis

4. Frequency of food poisoning is increasing! more fresh fruit/vegetables more pre-cooked foods more kinds of food 5,000 deaths, 325,000 hospitalizations, 76 million illnesses FDA resources can’t keep up! Food Poisoning

5. E. coli Clostridium Staphylococcus Campylobacter Yersinia Listeria Vibrio Salmonella Bacillus Eating Contaminated Stuff Causes You Lots of Very Smelly Barf Food Poisoning

6. Staphylococcus Salmonella Shigella Campylobacter E. coli Yersinia Vibrio Bacillus Listeria Clostridium The bugs: Food Poisoning

7. gram-positive cocci enterotoxins made in food survive high temps nose, skin Staphylococcus Food Poisoning

8. Staphylococcus on blood agar plate

9. Staphylococcus

10. Staphylococcus surrounding hair shaft

12. gram-negative rod motile injects proteins, causing “ruffles” replicates in host cells sensitive to stomach acid Salmonella Food Poisoning

13. Salmonella

15. Ruffles

22. gram-negative rod microaerophilic likes warm places C. jejuni (diarrhea), C. fetus (sepsis) cells eat bugs, then die monocytes can carry bugs into blood Campylobacter Food Poisoning

23. Campylobacter

27. gram-negative rod motile EHEC strains O and H antigens cytotoxins damage vessels E. coli Food Poisoning

28. E. coli

29. E. coli outbreak: raw spinach October 2006 3 died, over 200 became ill Traced to spinach grown in central California Grazing deer or water contaminated with cattle feces

31. E. coli outbreak: Taco Bell November-December 2006 70+ became ill Green onions vs. lettuce Contamination at packing plant ?

32. Diarrhea Hemolytic uremic syndrome (HUS) E. coli diseases Food Poisoning

33. hemorrhagic colitis

34. Microangiopathic hemolytic anemia

35. gram-negative rod grows in cold temperatures mesenteric lymphadenitis Yersinia Food Poisoning

36. Yersinia

37. Yersinia: “safety-pin” appearance

38. Plague

39. Y. pestis transmitted by tick

41. mesenteric lymphadenitis

44. gram-negative rod single flagellum likes water can tolerate acid makes toxins Vibrio Food Poisoning

45. Vibrio

52. gram-positive rod spores makes toxins (in food) Bacillus Food Poisoning

53. Bacillus

54. Bacillus: “box-car” appearance

55. Bacillus

58. gram-positive rod heat resistant hides out in host cell cytoplasm mild GI illness in most meningitis, sepsis in fetuses, elderly Listeria Food Poisoning

59. Listeria

60. Listeria inside neutrophil

62. gram-positive rod anaerobic spores toxins C. botulinum: progressive paralysis adults usually recover babies may not C. perfringens: diarrhea Clostridium Food Poisoning

63. Clostridium

67. beforeafter Botox 

69. enterocolitis self-limited, usually serious complications rare incubation time varies fever, tenderness on exam Clinical Food Poisoning

70. culture gram stain other tests Diagnosis Food Poisoning

71. Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

72. Important cause of death worldwide Here, more bothersome than deadly Three categories: secretory diarrhea invasive diarrhea antibiotic-associated diarrhea Non-Food-Related Diarrhea

73. loss of fluids, electrolytes from small intestine mild (traveler’s diarrhea) to severe (cholera) Definition Secretory Diarrhea

74. Enterobacteriaceae (E. coli, others) Vibrionaceae (Vibrio, Campylobacter) Pathogens Secretory Diarrhea

75. environment (vibrio) humans (salmonella) Reservoirs Secretory Diarrhea

76. Transmission fecal-oral route … feces, food, fluids, fingers, flies, fomites, fornication some bugs require only a small inoculum! No matter how clean we think we are… if sh*t was red, the world would be pink. Secretory Diarrhea

77. Pathogenesis proximal small intestine different bugs have different mechanisms Secretory Diarrhea

78. V. cholerae virulence genes switch on in intestine cholera toxin binds to epithelium, gets eaten toxin activates adenylate cyclase  cAMP →  Na + absorption,  Cl - excretion water moves into gut by osmosis, leading to diarrhea Secretory Diarrhea

79. normal enterocyteenterocyte in secretory diarrhea

80. ETEC Enterotoxins change fluid transport in the gut… …so instead of absorbing, the gut is secreting. like cholera toxin, but less serious Secretory Diarrhea

81. EPEC complex mechanisms – no toxin actin-rich pedestals beyond that, unclear mechanisms Secretory Diarrhea

82. Clinical most cases acute, self-limiting except V. cholera and EPEC illnesses, which can be fatal Secretory Diarrhea

83. Stool culture selective media differential media Further testing strains, virulence factors useful for epidemiology Secretory Diarrhea

84. Treatment usually not necessary except for which diseases? Secretory Diarrhea

85. Definition cause: bugs that invade the intestine result: bloody diarrhea or dysentery bugs: Shigella and EHEC Invasive Diarrhea

86. Shigella: characteristics gram-negative rod species:  S. dysenteriae (dysentery)  S. flexneri  S. boydii  S. sonnei (secretory diarrhea) Invasive Diarrhea

87. Shigella

89. Shigella: transmission person-to-person small inoculum! Invasive Diarrhea

90. Shigella: pathogenic features changeable phenotype! Acid-resistant in stomach, invasive in intestine Pure selfishness: whatever works best. Acidity turns on the genes for acid resistance! Invasive Diarrhea

91. Approach. Sneakiness. Eating. Prodding. Escape. Finger. Ulcer. Shigella: pathogenic features Invasive Diarrhea

93. Shigella

94. Shiga toxin stops protein synthesis decreases Na + absorption (watery stools) damages endothelial cells (bloody stools) worst result: HUS Shigella: toxin Invasive Diarrhea

95. Diseases caused by E. coli: Diarrhea Urinary tract infection Neonatal sepsis Gram-negative sepsis E. coli transmitted in DUNG-contaminated water Invasive Diarrhea

97. Enterohemorrhagic E. coli (EHEC): characteristics gram-negative rod many strains cause invasive diarrhea O (cell wall) and H (flagellar) antigens O157:H7 most common Invasive Diarrhea

98. EHEC: transmission food (beef, spinach, green onions…) small inoculum! Invasive Diarrhea

99. hemorrhagic colitis

100. microangiopathic hemolytic anemia

101. EHEC: pathogenic features toxins (inactivate RNA, like Shiga toxin) endothelial damage (toxin + cytokines) end result: bloody diarrhea and/or HUS Invasive Diarrhea

102. EHEC: diseases GI complications sometimes, asymptomatic often, bloody diarrhea (hemorrhagic colitis) usually resolves in a week HUS 1 in 10 people with severe diarrhea get HUS #1 cause of acute renal failure in children triad: MAHA, thrombocytopenia, renal failure can be fatal (especially in children, elderly) Invasive Diarrhea

103. Diagnosis stool exam stool culture fancy stuff Invasive Diarrhea

104. Common in hospitalized patients! Broad-spectrum antibiotics: reduce normal flora interfere with carb breakdown Clostridium difficile underlies most cases Antibiotic-Associated Diarrhea

105. Mnemonic for C. difficile infection: It’s diff icult to be in a clo set with someone having explosive foul-smelling diarrhea, because it smells and there is no air in there. Antibiotic-Associated Diarrhea

106. Bug characteristics gram-positive rod obligate anaerobe forms spores hard (‘difficile’) to grow! makes exotoxins Antibiotic-Associated Diarrhea

107. Clostridium

108. Pathology exotoxins cause cell death, shallow ulcers, pseudomembranes early lesions superficial may eventually invade Antibiotic-Associated Diarrhea

109. Pseudomembranous colitis

110. Epidemiology 30% of hospitalized patients! elderly at greater risk associated with antibiotics also with chemotherapy, enemas, enteric feeding spread patient to patient by hospital personnel Antibiotic-Associated Diarrhea

111. Disease severity wide spectrum asymptomatic to fulminant colitis usually: just diarrhea amount of toxin is unrelated Antibiotic-Associated Diarrhea

112. Forms of disease Diarrhea Pseudomembranous colitis Osmotic diarrhea Fulminant colitis Antibiotic-Associated Diarrhea

113. Diagnosis stool smear forget culture toxin detection scope dangerous Antibiotic-Associated Diarrhea

114. Treatment oral metronidazole vancomycin relapse: metronidazole severe disease: bowel resection Antibiotic-Associated Diarrhea