1. Lecture 17: Microbial diseases of the digestive system Edith Porter, M.D. 1

2. 2  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

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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 Microbes contribute to ~ 40% of the weight of feces 5

6.  Transmitted via food and water  Fecal-oral cycle can be broken by:  Proper sewage disposal  Disinfection of drinking water  Proper food preparation and storage 6

7.  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 7

8. 8 Teeth affected, begins on the teeth

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

10.  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 10

11. 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 11

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

13.  Food poisoning  Undercooked rice  Ingestion of bacterial exotoxin produces mild symptoms 13

14. 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 14

15.  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 15

16.  Refer to surface structures  H-antigen is part of flagella  O-antigen located on LPS  K or Vi- (Samonella) antigen - capsule  High antigenic variability 16

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19.  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 19

20. 20 DiseasedNormal

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22. Ingested Requires large dose (10 5 ) 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 22

23.  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 23

24. 24 Human to human Animal product to human

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

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

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

29.  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 29

30. 30  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.  Mumps  Gastroenteritis  Hepatitis 31

32. 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 32

33.  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 33

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

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37.  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 37

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41.  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 41

42. 42 Type of worm DiseasePathogenSymptoms Tapeworm (Cestodes) TaeniasisTaenia sagitina and T. solium Taenia live in the intestinal lumen, few symptoms. Eggs from T solium may be ingested and spread to brain Hydatid disease Echinococcus granulosus Larvae may spread into liver Round worm (Nematodes) PinwormEnterobius vermicularis Itching around anus HookwormNecator Ancylostoma Larvae enter skin and migrate to intestine Suck blood, anemia AscariasisAscarisAdults live in the intestine, few symptoms but may obliterate lumen TrichinellosisTrichinella spiralis Larvae in muscles, rarely fever, pain

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45.  Caries is a result from biofilm and plaque formation and acid production due to S. mutans and 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 Noro virus); protozoa (Giradia, Cryptosporidium, Entamoeba histolytica); helminths 45

46. 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) Giardia lamblia B) Escherichia coli C) Taenia spp. D) Vibrio parahaemolyticus E) Entamoeba histolytica 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. 46