MICR 201 Microbiology for Health Related Sciences

1. Lecture 17: Microbial diseases of the digestive system Edith Porter, M.D. MICR 201 Microbiology for Health Related Sciences

2. Lecture outline • Structure & function and normal microbiota of the digestive system • Bacterial diseases • Mouth: dental caries, periodontal disease • Lower digestive system: peptic ulcer disease, food poisoning, cholera, gastroenteritis, salmonellosis, typhoid fever, C. difficile antibiotic associated diarrhea • Viral diseases • Mumps, gastroenteritis, hepatitis • Fungal diseases • Ergot and aflatoxin poisoning • Protozoan diseases • Giardiasis, cryptosporidiosis, amoebiasis • Helminthic diseases • Tapeworm, pinworm, hookworm, ascariasis, trichinellosis

3. The human digestive system

4. Healthy human tooth

5. >700 species in mouth Viridans strepotcocci Many anaerobes Spirochaetae No only bacteria Few in the stomach due to low pH Few in small intestine due to special defense cells Large numbers in large intestine, including: Lactobacillus Enterococcus E. coli Enterobacter Klebsiella Proteus Bacteroides Normal microbiota in the gastrointestinal tract Microbes contribute to ~ 40% of the weight of feces

6. Transmission of microbial diseases of the digestive system • Transmitted via food and water • Fecal-oral cycle can be broken by: • Proper sewage disposal • Disinfection of drinking water • Proper food preparation and storage

7. Role of Streptococcus mutansand sucrose in dental caries • Oral bacteria convert sugars to acid • Acid damages tooth enamel • Most cariogenic is S. mutans • Biofilm and subsequently plaque formation • Chewing sugar free gum reduces caries

8. Stages of dental caries (tooth decay) Teeth affected, begins on the teeth

9. Periodontal disease • Gums affected in-between the teeth • Inflammation and degeneration of structures that support teeth

10. Bacterial diseases of the lower digestive system • Chronic • Peptic ulcer caused by H. pylori • Intoxication (food poisoning) caused by ingestion of toxin • Symptoms appear 1-48 h after ingestion • Treated with fluid and electrolyte replacement • Infection caused by pathogen multiplying in the intestine and producing various toxins • Incubation from 12 h to 2 weeks • Symptoms usually include diarrhea, gastroenteritis, dysentery • Treated with fluid and electrolyte replacement

11. Helicobacter pylori • Causes peptic ulcer disease • Produces urease (urea  carbon dioxide + ammonia, increases pH), a cytotoxin, and continuously attracts and activates neutrophils • Urease detection used in rapid assays • Treated with antibiotics • Chronic H. pylori infection may lead to stomach cancer

12. Staphylococcal food poisoning • Staphylococcus aureus enterotoxin is a superantigen • In intestine, it acts as neurotoxin • Nausea, vomiting

13. Bacillus cereusgastroenteritis • Food poisoning • Undercooked rice • Ingestion of bacterial exotoxin produces mild symptoms

14. Cholera • Caused by Vibrio cholerae serotypes that produce cholera toxin • Infection rate higher in individuals with impaired gastric acid production • Toxin causes host cells (enterocytes) to secrete electrolytes and water • 12 – 20 L, rice water stool • Toxin does not destroy the enterocyte, no inflammation and no fever

15. Gastroenteritis caused by enterobacteriaceae • Most important genera • E. coli • Salmonella • Shigella • Yersinia • Identified biochemically and by serotyping with antisera specific for certain surface structures • Symptoms depend on toxin produced • Enterotoxin: cholera like, watery diarrhea (E. coli) • Cytotoxin (shiga toxin) bloody diarrhea with inflammation, fever (E. coli, Shigella) • Endotoxin mediated: general inflammation, fever • Dysentery: diarrhea with leukocytes in stool as sign of a severe inflammation, accompanied by fever and possibly blood

16. O- antigens, H- antigens and K- antigens in enterobacteriaceae • Refer to surface structures • H-antigen is part of flagella • O-antigen located on LPS • K or Vi- (Samonella) antigen - capsule • High antigenic variability

17. E. coli gastroenteritis

18. Various types of damage to intestinal cells by E. coli

19. Pathogenesis of hemolytic uremic syndrome caused by EHEC O157:H7 • Certain strains produce shiga like toxin • Toxin is resorbed and enters circulation • Bacteria remain in the intestine on top of the cells, not inside • Toxin is transported to small vessel • Microvascular endothelial cell damage • Inhibition of protein synthesis • Apoptosis • Platelet activation

20. Kidney damage in hemolytic uremic syndrome Normal Diseased

22. Salmonellosis • Ingested • Requires large dose (105) • Sources include chicken and reptiles like turtles • Salmonella enterica serovars such as S. enterica Typhimurium • Affects small intestine • Mortality (<1%) due to septic shock caused by endotoxin • Systemic in immunocompromised

23. Typhoid Fever • Salmonella enterica Typhi • Human adapted • Low infectious dose (~1000) • Enter through small intestine • Bacteria routinely spread throughout body in phagocytes • High fever, continued headaches • Diarrhea only during 2.. and 3. week when fever declines • 1-3% recovered patients become chronic carriers, harboring Salmonella in their gallbladder

24. Incidence of Salmonellosis and typhoid fever Animal product to human Human to human

25. Major pathogenic factors of Salmonella • Two component signal transduction • Sensor and response regulator • Type III secretion apparatus • Injects proteins directly into host cell • “Hypodermic needle” • Injected proteins cause host toengulf bacterium, prevent fusion of salmonella vacuole with lysosomes, cause diarrhea Induced uptake and intracellular survival in macrophages and enterocytes

26. Shigellosis • Shigella spp. producing Shiga toxin (cytotoxin) • Affects colon • Shiga toxin causes inflammation and bleeding, diarrhea • Dysentery with leukocytes in stool • Typically no systemic spread

27. Invasion of epithelial cells by Shigella

28. Yersiniagastroenteritis • Y. enterocolitica and Y. pseudotuberculosis • Can reproduce at 4°C • Usually transmitted in meat and milk • Associated with arthritis

29. Campylobactergastroenteritis • Campylobacter jejuni • Microaerophilic gram negative rods (not member of enterobacteriacea) • Usually transmitted in cow's milk • Linked to Guillian-Barre syndrome, an autoimmune neurological disorder with temporary paralysis

30. Clostridium difficile-associated diarrhea • C. difficile is part of normal microbiota in large intestine • Proliferates and secretes toxins when patient takes antibiotics • Toxins destroy epithelial cells, induce diarrhea , and attract neutrophils • Pseudomembranous enterocolitis • Recently, transmission in hospitals noted

31. Viral diseases of the digestive system • Mumps • Gastroenteritis • Hepatitis

32. Mumps • Mumps virus • Enters through respiratory tract • Infects parotid glands and leads to painful swelling and fever • May cause orchitis (infection of the testis that may lead to infertility), even less frequently meningitis, inflammation of ovaries, and pancreatitis • Prevented with MMR vaccine

33. Viral gastroenteritis • Rotavirus • 3 million cases annually • 1-2 day incubation, 1 week illness • Norovirus • 50% of U.S. adults have antibodies • 1-2 day incubation. 1-3 day illness • Treated with rehydration

34. Hepatitis • Inflammation of the liver • Hepatitis may result from drug or chemical toxicity, EB virus, CMV, or the Hepatitis viruses

35. Hepatitis viruses

36. Liver cirrhosis as complication of hepatitis

37. Protozoan diseases of the digestive system • Giardia • Flagellated • Duodenal infection, prolonged symptoms, may interfere with food absorption • Duodenal fluid is used for diagnosis • Cryptosporidium • Numerous stools, cholera like, weight loss • Often in AIDS patients • Acid fast cysts in stool are diagnostic • Entamoeba • Uptake of cysts with are activated by stomach acid • Severe dysentery with bloody diarrhea (E. histolytica) • Amoeba (not cysts) with ingested erythrocytes in stool is diagnostic

38. Giardialamblia

39. Cryptosporidiosis

40. Entamoebahistolytica

41. Fungal diseases of the digestive system: toxin mediated • Mycotoxins • Produced by some fungi • Claviceps purpurea • Grows on grains • Produces ergot (LSD like) • Toxin restricts blood flow to limbs; causes hallucination • Aspergillus flavus • Grows on grains • Produces aflatoxin • Toxin causes liver damage; liver cancer

42. Main characteristics of helmintic diseases of the digestive system

43. Hookworms attach firmly to the intestinal mucosa and may cause anemia

44. Ascaris may obliterate the intestinal tract

45. Important to remember • Caries is a result from biofilm and plaque formation and acid production due to S. mutansand other bacteria • Differentiate food poisoning with ingestion of preformed toxin from gastroenteritis due to pathogens proliferating in the intestine that may produce enterotoxins (watery diarrhea) or cytotoxins (bloody diarrhea with dystentery) • Food poisoning: enterotoxins from S. aureus, B. cereus • Gastroenteritis due to bacterial obligate pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Cholera); bacterial opportunistic pathogens (some E. coli strains); viruses (Rota virus and Norovirus); protozoa (Giradia, Cryptosporidium, Entamoebahistolytica); helminths

46. Check your understanding 1) Which of the following statements about salmonellosis is false? A) It is a bacterial infection. B) It requires a large infective dose. C) A healthy carrier state exists. D) The mortality rate is high. E) It is often associated with poultry products. 2) Which of the following feeds on red blood cells? A) Giardialamblia B) Escherichia coli C) Taenia spp. D) Vibrioparahaemolyticus E) Entamoebahistolytica 3) Most of the normal microbiota of the digestive system are found in the A) Mouth. B) Stomach. C) Small intestine. D) Large intestine. E) C and D.