Lecture 21 Campylobacter and helicobacter Flashcards
What are some shared characteristics?
-Gram-negative helical rods
-Epsilonproteobacteria
-common bacterial pathogens, but only recently discovered
-microaerophilic and fastidious
-infect GI tract of humans and animals
flagellar motility
-molecular mimicry
What are the two flagella motility?
-Cj-Bipolar-darting
Hp-lophotrichous-penetration of mucous
What is the molecular mimicry of theses cells?
• LPS/LOS structures that mimic host glycosylation
What genus of Campylobacter cause majority of foodborne bacterial infections?
- C. Jejuni (most)
- C. coli
- low infectious dose
What are some sx of C jejuni dx?
• Enteritis: diarrhea (sometimes bloody - dysentery), fever, abdominal pain, inflammation
- 1-7 days after exposure
- self limiting
What can happen ifC Jejuni becomes extaintestinal?
– Biliary tract
– Bacteremia
– Meningitis
– Others
How is C jejuni treated?
-fluids electrolytes
-in severe cases abx
-resistance problem
Ciprofloxacin, azithromycin
How is C jejuni dx?
- Cx (gold standard)
- darting motility in stool sample
- serum serology and PCR tests
What are the cases of C jejuni?
most sporadic zoonosis
- poultry
- pets
some can cause outbreaks, Raw milk, untreated water in warmer months
What is the pathogenesis of C jejuni?
- Adheres to intestinal epithelial
- Cytolethal distending toxin
- cell cycle arrest, growth but do not divide
- Endocytosis/transcytosis (immune evasion, gain access to underlying tissues, requires Tubulin not actin)
What are the virulence factors of C jejuni?
- Motility (polar flagellum, darting)
- Chemotaxis- mucins and glycoproteins, repelled by bile
- Adhesion and invasion (zipper trigger)
- capsule
- iron uptake
- stress respones
- antimicrobial resistance
- LPS/LOS
What is cytolethal distending toxin (CDT)?
-AB2 type toxin
-found in gram -
activates ATM, causing apoptosis
What does Cj infection do?
promot colonization
- increase inflammation
- may promote immune evasion
What is Cuillain-Barre syndrome?
- ascending paralysis caused by C jejuni
- anti-GM1 and anti GD1a IgG (expressed in nervous system)
- serotype O:19 and O:41 responsible
- 90 percent recover
What is reactive arthritis?
- caused by C Jejuni
- Caused by enteric pathogens like Slamonella, Shigella, or chlamydial infection
- molecular mimicry
- treatments for sx,
- 2/3 self limited, chronic arthritis in unresolved
What is C fetus?
extraintestinal disease causing
- in cattle, sheep, reptiles
- can cause diarrheal illness, but more associated with invasive disease
- S- layer resistant to complement
- infection during pregnancy can cause fetal loss, neonatal sepsis (also in C jejuni infection)
When and how was H pylori discovered?
100 years ago as spirochetes in canine gastric mucosa, cannot compete in lower level tract, only in stomach
What are some distinguishing things about H. pylori?
- originally part of campylobacter, then helicobacter was created
- Bacterial carcinogen (Stomach cancer)
- occurs early in life and can persist
- infects humans and non-human primates
- no known environmental reservoir
- gastro to oral
what are H pylori diseases?
- asymptomatic gastritis
- ulcers (gastric, duodenal)
- gastric adenocarcinoma
- MALT lymphoma
What is H pylori gastritis?
- asymptomatic
- parietal cells depleted (secrete HCl acid for stomach)
- neutrophils infiltrate
- pro inflammatory cytokines
What can H pylori cause in the stomach?
ulcers
What are two types of cancers caused by H pylori?
- gastric adenocarcinoma
- MALT lymphoma
How is a gastric ulcer formed from H pylori?
Corpus predominant atrophic gastritis
How is a MALT lymphoma formed from H pylori?
Nonatrophic pangastritis
How is duodenal ulcer formed from H pylori?
Antral-predominant gastritis
How is gastric cancer caused by H pylori?
Corpus-predominant atrophic gastritis, intestinal metaplasia, dysplasia, gastric cancer
How is H pylori dx?
- Urea breath test (carbon isotope)
- stool antigen test
- serological tests (anti-H pylori IgG)
- Endoscopy and biopsy (culture histology)
How is H pylori treated?
- no sx- don’t treat
-combination therapy
-treatment failure can occur:
resistance, pH effect on drugs, non-compliance
What can be used as combination therapy for H pylori?
– 2 antibiotics (tetracycline, metronidazole, clarithromycin, amoxicillin)
– drug to reduce acid (ranitidine, cimetidine, famotidine, omprazole, pantoprazole, lansoprazole, bismuth)
• improve symptoms
• increase efficacy of antibiotics
– Bismuth
• Promotes mucosal healing • Has antibacterial properties
What is the pathogenesis of H pylori?
- Majority of bacteria in mucus layer overlying gastric epithelium
- Urease enzyme to locally buffer acid
- flagellar motility to get epithelium
- adherence to epithelium
- toxins
What are the toxins of H pylori?
- Vac A- Cell damage
- Nap -recruit immune cells
- Cag A- subvert host cell signaling
What are the virulence factors of H pylori?
- adhesins (BabA, SAbA)
- Molecular mimicry
- Vac A (vaculolating cytotoxin)
- Cag pathogenenicity island
What is Vac A in H pylori?
- auto transporter
- isolates have different alleles with different activities
- induces cells to fill up with big vacuoles-cytostatic
- increase permeability of epithelium
- can induce apoptosis via interaction with mito
- inhibits T cells
What is Cag pathogenicity island?
- associate with ulcer, cancer
- Type IV secretion system
- induce proinflammatory cytokines
- Translocation of CAgA to host
What is an upside to H pylori?
immune modulation may protect against allergies and chronic inflammatory disorders
