Topic 1-12 (Lecture 12) Flashcards
What are the general characteristics of Vibrio cholerae?
i.e motility, Gram pos/neg, Shape, external features
Motile
gram-negative
Curved rod (vibriod)
Single, polar flagellum
Where are vibrio cholerae found?
Survive in humans, fresh or brackish water
Vectors of cholera?
Only humans; no insect vector or animal reservoir
How are V. cholerae strains serotyped (identified)?
Based on LPS O antigen
What serogroups of V. cholerae are responsible for cholera outbreaks?
O1 and O139 serogroups
What are the major virulence factors of V. cholerae?
Cholera toxin
Tcp pili
Flagellum (motility)
How is cholera spread?
oral ingestion of fecal-contaminated water & food (fecal-oral route) (often linked w/ poor sanitation);
How often does the disease tend to appear?
Appears in epidemics
What type of individuals are susceptible to cholera?
All individuals are susceptible; however, those with damaged/underdeveloped immunity, reduced gastric acidity, or malnutrition may suffer from more severe forms of the illness
What is the incubation period of chloera?
6 hours to 5 days
What causes the disease?
An enterotoxin (type of exotoxin) called cholera toxin (CT) which causes massive diarrhea (loss of 20L/day of fluids)
What are the symptoms?
Watery diarrhea containing mucus, epithelial cells (“rice-water stool”) and lots of bacterial vibrios (cell shape is vibroid)
What are complications associated with diarrhea caused by cholera?
Severe fluid and electrolyte loss → dehydration, anuria (lack of urination), acidosis (in blood), and shock
Possible muscle cramping, nausea, vomiting ,fever
Loss of K+ ions leading to possible cardiac complications and circulatory failure
How is cholera diagnosed?
Gastrointestinal symptoms
Presence of rice water stool
Confirmation by isolation of Vibrio cholarae from stool (Think of Koch’s postulates)
What is the main potent toxin of V. cholorae?
Cholera toxin (CT) Those who do not produce CT may still cause disease, but a milder form that is caused by other toxins
What is the structure of CT? (cholera toxin)
Multimeric protein consisting of 5 identical binding proteins (“B”) and one enzymatic subunit (“A”) - thus called an AB5 toxin
What is the action of the AB5 toxin? (in steps)
1) A B subunit binds to GM1 ganglioside (a glycolipid receptor) on an intestinal epithelial cell membrane
2) CT endocytosis and passes through endomembrane (To golgi, to ER) where A portion enture cytosol
3) A unit activates adenylate cyclase which converts ATP to cAMP
4) cAMP stimulates protein kinase A (PKA) which phsophorylates cystic fibrosis transmembrane regulator (CFTR)
5) CFTR stimulates secretion of Cl- ions, which further stimulate K+ and bicarbonate ions (due to osmosis)
6) Change in ion concentration due to electrolyte loss results in water entering lumen through via osmosis
7) Toxin-damaged cells become pumps for water and electrolytes (constantly being replenished via blood flow) resulting in diarrhea, dehydration, and the massive loss of electrolytes
What host defence plays a large role in preventing cholera infection?
Gastric acidity; V. cholarae are sensitive to acid pH
What are implications of V. cholerae’s acid intolerance?
Large ID50 required to produce disease (since gastric acidity can kill the bacteria)
Those with poor health or gastric abnormalities are more easily infected
Consumption of food or antacid may provide protection of the bacteria (by raising pH)
What area of the body is the V. cholerae well adapted to survive in?
Small intestine
What adaptations help V. cholerae colonize the small intestine?
Resistant to bile salts
Can adhere to & penetrate mucous layer of small intestine
WIthstand propulsive gut motility (peristalsis of gut to move food along) using its motility and chemotaxis against gut mucosa
What determinants affect the colonization of V. cholerae?
Tcp (toxin co-regulated pili) that appears to cause aggregation of bacteria (bacteria w/o tcp are not pathogenic) acf genes (accessory colonization factor) may be required to mediate binding
How is cholera treated?
Rapid replacement of fluids, either through oral rehydration w/ water, salts and glucose mix (like Gatorade) or via intravenous re-hydration therapy for those in shock or unable to drink
Are antibiotics useful against cholera?
May be helpful, but not essential - lost in stool anyways. Only help to reduce duration by reducing CT production, stool volume, and shedding of vibrios
