Lecture 22 -Helicobacter-Campylobacter-ELMS

Lecture 22 -Helicobacter-Campylobacter-ELMS - Helicobacter...

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Unformatted text preview: Helicobacter Lecture 22 Classification Classification Family Genus Species Helicobacteraceae Helicobacter >20 species H.pylori History of a discovery History of a discovery Helicobacter pylori The Nobel Prize in Physiology or Medicine 2005 “The greatest obstacle to knowledge is not ignorance, it is the illusion of knowledge.” Daniel Boorstein ­ Historian Ulcers may lead to bleeding Blood may appear in vomit and stool Historical evidence of bacteria in Historical evidence of bacteria in stomach!! J.R. Warren's contribution J.R. Warren's contribution First linking of bacteria with ulcers via histopathology/Electron microscopy of patient’s stomach samples Marshall’s contributions Marshall’s contributions Do antibiotics heal Do antibiotics heal gastroenteritis? More historical evidence More historical evidence H.pylori susceptible to Bismuth H.pylori Bismuth + Antibiotic showed 75% cure rate Validation Validation Acceptance Acceptance 1979 Initial report (J.R. Warren) 1994 General acceptance Epidemiology Epidemiology Epidemiology Epidemiology 9 out of ten ulcers caused by H. pylori 25 million Americans suffer from ulcers (~10% of population) Transmission Transmission H. pylori is contagious, although the exact route of transmission is not known. Person­to­person transmission by either the oral­oral or fecal­ oral route is most likely Consistent with these transmission routes, the bacteria have been isolated from feces, saliva and dental plaque of some infected people Transmission occurs mainly within families in developed nations yet can also be acquired from the community in developing countries H. pylori may also be transmitted orally by means of fecal matter through the ingestion of waste­tainted water, so a hygienic environment could help decrease the risk of H. pylori infection Disease Manifestation Disease Manifestation Gastric (stomach) and also pancreatic cancer General Characteristics: H.pylori General Characteristics: Gram­neg. Spiral/helix shape (but can change to coccoid in culture) Motile, multiple polar flagella (lophotrichous) H.Pylori Culture 37OC optimal growth temperature Microaerophilic atmosphere (Campylobacter!) 5­7% Oxygen (20%) 5­10% CO2 (0.05%) Pathogenicity: Urease Pathogenicity: Urease Neutralization of stomach pH Neutralization of stomach pH (microenvironment) Reacts with another H+: HCO3­ + H+ ↔ CO2 + H20 Diffuses into blood stream + Detected by breath test Pathogenicity: pH; in stomach Pathogenicity: pH; in stomach Intracellular H.pylori Intracellular H.pylori Most bacteria remain extracellular and colonize the stomach epithelium Some penetrate epithelial cells and have to deal with phagocytes (macrophages) of the host immune system Pathogenicity: pH; inside Pathogenicity: pH; inside macrophages VacA forms Cl­channel in host cell phagosome and disturbs the osmolarity of the phagosome, resulting in influx of water and formation of megasomes VacA pore structure Megasomes LPS Type 4 SS (injects effectors into host cell) Adhesins (VacA, SabA, BabA) Flagella CagA pathogenicity island ­encodes T4SS ­encodes CagA protein which disrupts intercellular junctions VacA exotoxin ­adhesin, induces epithelial cell death, inhibits phagosome maturation, inhibits T­cell activation Pathogenicity factors Pathogenicity factors Diagnosis Diagnosis Breath tests: ­drink labeled substrate of Urease ­ detect increase CO2 in breath of individual with H. pylori Endoscopy: ­small sample of stomach lining is taken, Urease test Serology: detects antibodies against bacteria (problem: current or past infection?) ELISA: detects H.pylori antigens in stool of patients (only positive if current infection) Breath Test Breath Test 14 C or 13C CO2 Patients swallow urea labelled with an uncommon isotope, either radioactive carbon­14 or non­radioactive carbon­13. In the subsequent 10­30 minutes, the detection of isotope­labelled carbon dioxide in exhaled breath indicates that the urea was split; this indicates that urease (the enzyme that H. pylori uses to metabolize urea) is present in the stomach, and hence that H. pylori bacteria are present. For the two different forms of urea, different instrumentation is required; carbon­14 is normally measured by scintillation, carbon­13 by isotope ratio mass spectrometry (IRMS). For carbon­13 a baseline sample before taking urea is required for comparison with the post urea sample. Treatment/Prevention Treatment/Prevention Combination of 2 antibiotics, anti­acid and bismuth for 2 weeks has cure rate of 90% No vaccine available Route of transmission little understood Campylobacter Lecture 22 Classification Classification Family Genera Species Campylobacteraceae Campylobacter C.Jejuni C. Coli C.upsaliensis General Characteristics General Characteristics Small (0.2­0.5um), gram­negative Curved, coma shaped rods (sometime spiral) microaerophilic growth requirements! motile Capsule LPS\LOS (O­antigen) and Flagella (H) and Capsule (K) antigens (for serum ID (serogroups) 42OC optimal growth temperature (poultry) ­used to enrich C.jejuni in cultures of stool samples Microaerophilic atmosphere 5­7% Oxygen (20%) 5­10% CO2 (0.05%) Filter (0.45um) samples before culture Include antibiotics into medium (e.g.: TMS, vancomycin) C.jejuni Culture Epidemiology Epidemiology Most common cause of bacterial gastroenteritis (more than Shigella and Salmonella combined) Estimated 2million infections per year (does not include C. upsaliensis, not easily detected) Most cases are sporadic events (not outbreaks!) and not reported to CDC 95% caused by C.jejuni ; 2­5% by C. coli Throughout the year but most common in Epidemiology/Transmission Campylobacter Natural reservoir (poultry, pigs, dogs cats birds) Zoonotic infection (poultry) Spread by consumption of contaminated food, unpasteurized milk and contaminated water (~80% of supermarket chicken C. jejuni positive!!) Bacteria do not multiply in food! Low infectious dose (500­1000) No person­to­person spread Gastroenteritis: Acute enteritis (2­5days after exposure), diarrhea (can be bloody) malaise, fever, abdominal pain Lasts about one week Bacteremia: 1.5 cases per 1000 intestinal infections Guillan­Barré Syndrome: Complication of infection Autoimmune like disease of peripheral nervous system Pain, weakness, and paralysis of extremities Recovery requires weeks to months Clinical Manifestation Clinical Manifestation Campylobacter Pathogenesis Pathogenesis Research Little understood (no good animal model) ­chicken and mouse do not reflect human pathology ­ferrets have been used (no tools; antibodies, cytokines, knock­out animals) Genome sequencing, signature­tagged mutagenesis, genetic tools for introducing and deleting specific genes Pathogenesis Pathogenesis Type 4 SS (encoded by virulence plasmid) Flagellum (important for motility, adhesion and protein secretion!) Lipooligosaccharide (LOS) involved in adhesion, serum resistance, autoimmune disease Cytolethal distending toxin CDT (trimer, CdtA, CdtB and CdtC that inhibits cell cycle progression, leading to cell death) Capsule Type IV secretion system Type IV secretion system Similar to type III SS, but contain conjugative pilus (DNA transfer) Diagnosis Diagnosis Microscopy is insensitive Culture on specialized media (including antibiotics) under microaerobic conditions using elevated temperature (42°C) Biochemical tests (catalase, oxidase , Hippurate positive) No good serodiagnostic tools available Treatment/Prevention Treatment/Prevention Treatment: Gastroenteritis usually self limiting, treat symptoms (Fluid and electrolyte loss) Antibiotics: use erythromycin Prevention: No vaccine available Proper preparation of food (poultry) Pasteurization of milk Control water supplies (Chlorine treatment) ...
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This note was uploaded on 01/24/2011 for the course BSCI 424 taught by Professor Staff during the Fall '08 term at Maryland.

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