Microbial Diseases Of The Digestive System PDF

MICROBIAL DISEASES OF THE DIGESTIVE SYSTEM GASTROINTESTINAL MICROBIOME, BACTERTIAL GASTROENTERITIS A N D I N TOX I C AT I O N Prepared by: BMS 150 Nick Inglis, Ph.D. IN A 24 HOUR PERIOD… ~200,000,000 people have gastroenteritis/day The amount of diarrheal water passed = the volume of wa...

MICROBIAL DISEASES OF THE DIGESTIVE SYSTEM GASTROINTESTINAL MICROBIOME, BACTERTIAL GASTROENTERITIS A N D I N TOX I C AT I O N Prepared by: BMS 150 Nick Inglis, Ph.D. IN A 24 HOUR PERIOD… ~200,000,000 people have gastroenteritis/day The amount of diarrheal water passed = the volume of water passing over Victoria falls in 1 minute 65,280,000L!!!!  1170 bacterial species!! GASTROINTESTINAL Viridans streptococci MICROBIOME ~free of microbes Anerobic environment; 30 trillion bacteria! Bacteroides Lactobacillus Eschericihia Enterobacter Proteus Klebsiella  1170 bacterial species!! GASTROINTESTINAL Viridans streptococci MICROBIOME ~free of microbes Anerobic environment; 30 trillion bacteria! Bacteroides Lactobacillus Eschericihia Enterobacter Proteus Klebsiella VIRIDANS STREPTOCOCCI Bacterial endocarditis  1170 bacterial species!! GASTROINTESTINAL Viridans streptococci MICROBIOME ~free of microbes Anerobic environment; 30 trillion bacteria! Bacteroides Lactobacillus Eschericihia Enterobacter Proteus Klebsiella CONSEQUENENCES OF INTESTINAL MICROBIOTA Review Microbial Antagonism Vitamin production (B12, folic acid, biotin and vitamin K) Produce 500mL/day of flatus BACTERIAL GASTROENTERITIS: COMMON FEATURES World-wide, endemic disease Associated with: poorly prepared foods, contaminated water, poor living conditions Common signs/symptoms: nausea, vomiting, diarrhea, loss of appetite, abdominal pain/cramping Diagnosis: signs/symptoms, nucleic acid test. BACTERIAL GASTROENTERITIS: TREATMENT Fluid replacement (drinking water, OTC electrolyte solutions like Gatorade) Some patients may need medication to suppress nausea if fluids can’t be taken (IV fluid sometimes required) Most symptoms disappear within hours or days; recovery from dehydration => 1 week GATORADE AS A MEDICATION?? BACTERIAL GASTROENTERITIS: PREVENTION BACTERIAL GASTROINTERITIS 1. CHOLERA Causative agent: Vibrio cholerae (vibrios, gram -ve) Portal of entry: ingestion of contaminated water, or raw/undercooked seafood Signs/symptoms: rice-water stool BACTERIAL GASTROINTERITIS 1. CHOLERA Incubation: 2-3 days Susceptibility: endemic areas with poor sewage treatment Treatment: fluid and electrolyte replacement, antimicrobials (e.g., tetracycline)  Intestinal lumen A Cholera toxin Water follows binds to B electrolytes into membrane lumen. of epithelial CHOLERA cell. TOX I N I N INTESTINAL CELLS Portion Epithelial Cyclic AMP cell of toxin A1 stimulates (part of A) cell to enters cell. secrete Cl−, Na+, and other electrolytes. A1 is an enzyme that Adenylate activates makes adenylate cyclic AMP cyclase. (cAMP). BACTERIAL GASTROENTERITIS: 2. SHIGELLOSIS Causative agent: Shigella (gram –ve bacillus) Starts as infection of small intestine, causing diarrhea, but eventually proceeds to large intestine Incubation: ~7 days Treatment: antimicrobial drugs, vaccine in development  Shigella Shigella attaches to epithelial cell of colon. Epithelial cell Nucleus THE EVENTS OF SHIGELLOSIS  Shigella Shigella attaches to epithelial cell of colon. Epithelial cell Nucleus THE EVENTS Shigella triggers endocytosis. OF SHIGELLOSIS  Shigella Shigella attaches to epithelial cell of colon. Epithelial cell Nucleus THE EVENTS Shigella triggers endocytosis. OF SHIGELLOSIS Shigella multiplies in cytosol.  Shigella Shigella attaches to epithelial cell of colon. Epithelial cell Nucleus THE EVENTS Shigella triggers endocytosis. OF SHIGELLOSIS Shigella multiplies in cytosol. Actin fibers Shigella invades neighboring epithelial cells, thus avoiding immune defenses.  Shigella Shigella attaches to epithelial cell of colon. Epithelial cell Nucleus THE EVENTS Shigella triggers endocytosis. OF SHIGELLOSIS Shigella multiplies in cytosol. Actin fibers Shigella invades neighboring epithelial cells, thus avoiding immune defenses. Mucosal abscess An abscess forms as epithelial cells are killed by the infection.  Shigella Shigella attaches to epithelial cell of colon. Epithelial cell Nucleus THE EVENTS Shigella triggers endocytosis. OF SHIGELLOSIS Shigella multiplies in cytosol. Actin fibers Shigella invades neighboring epithelial cells, thus avoiding immune defenses. Mucosal abscess An abscess forms as epithelial cells are killed by the infection. Blood vessel Phagocyte Shigella that enters the blood is quickly phagocytized and destroyed. No bacteremia. BACTERIAL GASTROENTERITIS: 3. SALMONELLOSIS/TYPHOID FEVER Causative agent: Salmonella enterica (2000 serotypes/strains) Serotypes Typhi and Paratyphi cause typhoid fever Enteridis and Typhimurium cause most N. American cases Exposure via consumption of food or water contaminated with feces of a carrier 1/3rd of chicken eggs contain S. enterica  (Slide 2) Salmonella Salmonella attaches to epithelial cells lining Epithelial the small intestine. cell Nucleus THE EVENTS OF SALMONELLOSIS  (Slide 3) Salmonella Salmonella attaches to epithelial cells lining Epithelial the small intestine. cell Nucleus THE EVENTS OF Salmonella triggers SALMONELLOSIS endocytosis.  (Slide 4) Salmonella Salmonella attaches to epithelial cells lining Epithelial the small intestine. cell Nucleus THE EVENTS OF Salmonella triggers SALMONELLOSIS endocytosis. Salmonella multiplies within food vesicle.  Salmonella Salmonella attaches to epithelial cells lining Epithelial the small intestine. cell Nucleus THE EVENTS OF Salmonella triggers SALMONELLOSIS endocytosis. Salmonella multiplies within food vesicle. Salmonella kills host cell, inducing fever, cramps, and diarrhea.  Salmonella Salmonella attaches to epithelial cells lining Epithelial the small intestine. cell Nucleus THE EVENTS OF Salmonella triggers SALMONELLOSIS endocytosis. Salmonella multiplies within food vesicle. Salmonella kills host cell, inducing fever, cramps, and diarrhea. Capillary (blood vessel) Bacteremia: Salmonella moves into bloodstream. TYPHOID FEVER AND SALMONELLOSIS Cells of serotype Typhi can enter blood Phagocytosed but not ingested Carried to liver, spleen, bone marrow, gall bladder Semi-permanent infection established Salmonella shed in feces TYPHOID FEVER: SIGNS AND SYMPTOMS Increasing fever, headache, muscle pains, malaise, loss of apetite (> 1 week) “Rose Spot” Rash on abdomen Repeated gastroenteritis bouts Life-threatening complications: intestinal hemorrhage, perforation, kidney failure, peritonitis BACTERIAL GASTROENTERITIS: 4. CAMPYLOBACTER DIARRHEA Causative agent: Campylobacter jejuni Lipopoylsaccharide/Lipid A Adhesins Cytotoxins (exotoxins) CAMPYLOBACTER DIARRHEA: PATHOGENESIS/EPIDEMIOLOGY 81% of chickens carry Campylobacter. Virulence factors specifically allow for colonization of the jejunum, ileum and colon. Incidence: 1.3 million people per year Mortality: ~75 Complications: Guillain-Barre Syndrome (GBS), Irritable Bowel Sydrome (IBS), arthritis. BACTERIAL GASTROENTERITIS: 5. ANTIMIICROBIAL-ASSOCIATED DIARRHEA Severe form of diarrhea caused by use of broad spectrum antibiotics Very common in hospitals Best case: 5-10 clear, watery, foul smelling stools passed each day Worst case: >10 bloody stools per day caused by formation of intestinal pseudomembranes INTESTINAL PSEUDOMEMBRANES Lesions CAUSATIVE AGENT: CLOSTRIDIUM DIFFICILE C. DIFF PATHOGENESIS BACTERIAL FOOD POISONING (INTOXICATION) Food poisoning Bacterial gastroenteritis Bacterial intoxications (toxifications) BACTERIAL INTOXICATION: SIGNS AND SYMPTOMS General symptoms (mild → severe): - Nausea, vomiting, diarrhea, cramps, discomfort, bloating, loss of appetite, fever - Less common: weakness, headache, breathing problems. Dehydration from fluid loss Most cases are self-limiting and last no more than 24 hours. S. AUREUS ENTEROTOXINS ENTERTOXIN STRUCTURE Superantigens! Can stimulate large populations of T-cells ENTEROTOXIN FUNCTION PATHOGENESIS AND EPIDEMIOLOGY Outbreaks usually associated with picnics, school cafeterias or large social functions Several hours at room temperature required for S. aureus to grow and produce toxins. Epidemiology: ???? MICROBIAL DISEASES OF THE DIGESTIVE SYSTEM VIRAL DISEASES OF THE DIGESTIVE S Y S T E M ( P L U S B O N U S D E N TA L C AV I T I E S A N D M U M P S ) Prepared by: BMS 150 Nick Inglis, Ph.D. OTHER BACTERIAL GI INFECTIONS: HELIOBACTER PYLORI AND PEPTIC ULCERS Ulcer: erosion of the lining of stomach or duodenum. Can be perforations Symptoms: Nausea, vomiting (with “coffee grounds” in vomit), tar-like stools Long-term: bowel obstructions, internal bleeding H. PYLORI IN ULCER FORMATION Helicobacter pylori (neutralizes stomach acid) Layer of mucus Nucleus Epithelial cell Mucus- in stomach lining secreting cell Red blood cells in capillaries Bacteria invade mucus and attach to gastric epithelial cells. UREASE H. PYLORI IN ULCER FORMATION Helicobacter pylori (neutralizes stomach acid) Layer of mucus Nucleus Epithelial cell Mucus- Neutrophil Lymphocyte in stomach lining secreting cell Red blood cells in capillaries Bacteria invade mucus and attach to Helicobacter, its toxins, and gastric epithelial cells. inflammation cause the layer of mucus to become thin. UREASE H. PYLORI IN ULCER FORMATION Helicobacter pylori (neutralizes stomach acid) Layer of mucus Acidic gastric juice Nucleus Epithelial cell Mucus- Neutrophil Lymphocyte in stomach lining secreting cell Ulcer Red blood cells in capillaries Bacteria invade mucus and attach to Helicobacter, its toxins, and Gastric acid destroys epithelial cells gastric epithelial cells. inflammation cause the layer of and underlying tissue. mucus to become thin. UREASE DENTAL CARIES/GINGIVITIS DENTAL CARIES – SIGNS/SYMPTOMS  Plaque DENTAL CARIES: CAUSATIVE AGENT Streptococcus mutans Dextran Dental plaque DENTAL CARIES DENTAL CARIES – DIAGNOSIS/TREATMENT Visual inspection during routine dental checkups Probing with sharp objects and X-rays can reveal cavities before observable pits form Treatment: remove the softened tissue from cavity and replace the hole with silver, gold, porcelain, or resin ROOT CANALS  DENTAL CARIES - EPIDEMIOLOGY N. American adults (20-64 y.o.) – 92% have had dental caries (to permanent teeth!); 42% of children (2-11) have at least one. Causes: - Diets high in sucrose (table sugar) - Continual snackingz Mumps Causative Agent: Rubulavirus (unenveloped, -ssRNA virus) Portal of entry: mucus membranes of upper respiratory tract Signs and Symptoms: parotitis, face pain, fever, headache, sore throat Incubation: 12-24 days LET’S BRING THE LECTURE BACK FULL CIRCLE! VIRAL GASTROENTERITIS ~200,000,000 people have gastroenteritis/day The amount of diarrheal water passed = the volume of water passing over Victoria falls in 1 minute 65,280,000L!!!! ROTAVIRUS primary cause of diarrheal illness in infants world-wide (30-50%) segmented dsRNA genome infects nearly every child in the world infections peak in winter 800k deaths/year (5% of all mortality < 5 yr old) GLOBAL DISTRIBUTION OF ROTAVIRAL DEATHS (~2014) R OTAV I R U S PATHOGENESIS OF ROTAVIRUS transmitted by fecal-oral contamination 10-100 infectious particles sufficient infants