Vibrio, Campylobacter & Helicobacter Flashcards
1
Q
Vibrio genus
A
- Vibrios are curved, gram-negative rods commonly found in saltwater
- Grow under aerobic or anaerobic conditions (facultative)
- Major pathogenic species are
- V. cholerae
- V. vulnificus
- V. parahemolyticus
- V. alginolyticus
2
Q
V. cholerae
A
- Causative agent of the diarrheal disease cholera. Intestinal fluids are released in voluminous bowel movements, which eventually lead to dehydration and electrolyte imbalance.
- These effects come from the action of cholera toxin secreted by Vibrio cholerae in the intestinal lumen.
- Despite the profound physiologic effects, there is no fever, inflammation, or direct injury to the bowel mucosa
3
Q
V. cholerae Growth and Structure
A
- V. cholerae has a low tolerance for acid, but grows under alkaline (pH 8.0 to 9.5) conditions
- Distinguished from other vibrios by its biochemical reactions, lipopolysaccharide (LPS), O antigenic structure, and production of cholera toxin (CT).
- Over 200 O antigen serotypes, only two of which (O1 and O139) cause the disease cholera.
- All strains capable of causing cholera also produce a colonization factor known as the toxin-coregulated pilus (TCP) because its expression is regulated together with CT.
- In aquatic environments cells may enter a dormant state and polysaccharide biofilms are produced
4
Q
V. cholerae Cholera Toxin
A
- CT is an AB type ADP-ribosylating toxin. Its molecule is an aggregate of multiple polypeptide chains organized into two catalytic subunits (A1, A2) and five binding (B) units. The B subunits bind to a GM1-ganglioside receptor found on the surface of many types of cells. Once bound, the A1 subunit enters the cell where it exerts its effect on the membraneassociated adenylate cyclase system.
- Target of the toxic A1 subunit is a guanine nucleotide (G) protein (Gsa) that regulates activation of the adenylate cyclase system.
- CT catalyzes the ADP-ribosylation of the G protein, rendering it unable to dissociate from the active adenylate cyclase complex.
- Causes persistent activation of intracellular adenylate cyclase which stimulates the conversion of ATP to cyclic adenosine 3’, 5’-monophosphate (cAMP).
- Accumulation of cAMP at the cell membrane causes hypersecretion of chloride, potassium, bicarbonate, and associated water molecules out of the cell into the intestinal lumen
5
Q
Cholera Epidemiology
A
- Epidemic cholera is spread primarily by contaminated water under conditions of poor sanitation.
- Endemic in the Indian subcontinent and Africa
- Convalescent human carriage is brief
- Short incubation period (two days) ensures that organisms ingested by others quickly enter the epidemic cycle (water supply).
- Modern travel makes imported cases possible
6
Q
Cholera Pathogenesis
A
V. cholerae’s colonization of the entire intestinal tract from the jejunum to the colon requires the organism to adhere to the epithelial surface by the TCP. The outstanding feature of V. cholerae pathogenicity is the ability of virulent strains to secrete CT which is responsible for the disease cholera. The water and electrolyte shift from the cell to the intestinal lumen is the fundamental cause of the watery diarrhea of cholera.
- Outpouring of fluid and electrolytes is greatest in the small intestine,
- Diarrheal fluid has approximately the same sodium content as plasma but also significant potassium and bicarbonate.
- Result is dehydration (isotonic fluid loss), hypokalemia (potassium loss), and metabolic acidosis (bicarbonate loss).
- Intestinal mucosa remains unaltered except for some hyperemia
- Expression of virulence factors is coordinated in a 2-component system. The process begins when a transmembrane regulatory protein (ToxR) “senses” environmental changes in pH, osmolarity, and temperature. ToxR then activates other regulatory proteins which direct the synthesis of TCP and CT whose genes are located in separate pathogenicity islands (PAIs).
7
Q
Cholera Manifestations
A
- Typical cholera has a rapid onset, beginning with abdominal fullness and discomfort, gurgling, rushes of peristalsis, and loose stools.
- The stools quickly become watery, voluminous, almost odorless. They contain mucus flecks giving a gross appearance called rice-water stools.
- There is no pus or blood in the stools and the patient is afebrile.
- Extensive fluid loss and electrolyte imbalance lead to extreme dehydration, hypotension, and death if untreated.
8
Q
Cholera Diagnosis
A
- A bacteriologic diagnosis is accomplished by isolation of V. cholerae from the stool.
- Requires use of special selective medium (thiosulfate-citrate-bile salt-sucrose [TCBS] agar).
- Clinical laboratories must be alerted to the suspicion of cholera especially outside the endemic areas.
9
Q
Cholera Treatment
A
•The outcome of cholera is dependent on balancing the diarrheal fluid and ionic losses with adequate fluid and electrolyte replacement.
-This is accomplished by oral and/or intravenous administration of solutions of glucose with near physiologic concentrations of sodium and chloride and higher than physiologic concentrations of potassium and bicarbonate.
•Antimicrobial therapy is secondary to fluid replacement.
-A single dose of azithromycin is optimal, but doxycycline, trimethoprim-sulfamethoxazole and fluoroquinolones are also effective.
10
Q
Cholera Prevention
A
- Epidemic cholera, a disease of poor sanitation, does not persist where treatment and disposal of human waste is adequate.
- As good sanitary conditions do not exist in much of the world, secondary local measures such as boiling or chlorination of water during epidemics are required.
- The cases associated with crustaceans can be prevented by adequate cooking (10 minutes) and avoidance of recontamination from containers and food preparation surfaces.
- Vaccines have been disappointing.
11
Q
V. vulnificus 3 Major Infections
A
- Acute gastroenteritis
- Necrotizing wound infections
- Invasive spesis
12
Q
V. vulnificus Acute Gastroenteritis
A
- Usually develops within 16 hours of eating contaminated (sea)food.
- Manifests as vomiting, diarrhea, and abdominal pain.
- Many patients develop distinctive bullous skin lesions.
13
Q
V. vulnificus Necrotizing Wound Infections
A
- Occur in broken or injured skin which is exposed to contaminated marine water (especially brackish water).
- Pathogen enters via the broken skin, and patients may develop a blistering dermatitis.
14
Q
V. vulnificus Invasive Sepsis
A
- The bacterium enters the systemic circulation directly from the GI tract or broken skin to produce bacteremia and septicemia.
- Invasion is characterized by the occurrence of blister-like skin lesions or bullae, and rapidly-spreading necrosis resembling necrotizing fasciitis.
- Invasive sepsis can occur after eating raw or undercooked shellfish, especially oysters.
- V. vulnificus is 80 times more likely to spread into the bloodstream in people with compromised immune systems, especially those with chronic liver disease.
15
Q
V. vulnificus Diagnosis
A
- Culture of organism from wound or hemorrhagic bullae is recommended
- All V. vulnificus isolates should be forwarded to a public health laboratory
- Blood cultures are recommended if the patient is febrile, has hemorrhagic bullae, or has signs of sepsis
- Marked left shift in WBC is common
- Renal injury with rising serum creatinine level is also common
- In severe infection, creatine kinase level is often elevated when necrotizing fasciitis or myonecrosis is present
30
Q
Helicobacter Gastritis Pathogenesis
A
In order to persist in the hostile environs of the stomach H. pylori employs multiple mechanisms to adhere to the gastric mucosa and survive the acid milieu of the stomach.
- Motility provided by the flagella allows the organisms to swim to the less acid pH locale beneath the gastric mucus
- Urease creates a more neutral pH microenvironment by ammonia production.
- At the mucosa adherence is mediated by surface proteins
- VACa: gastric mucosal injury
- CagA: disrupts host cell cytoskeleton, signaling and polarity (precursor to gastric cancer)
