35 - Bacterial Infections of the GI Tract III Flashcards
What is vibrio spp?
A bacteria that causes a non-inflammatory infection of the small intestine
There are three different types of this bacteria
What are the three different types of Vibrio spp.?
- Vibrio cholerae*
- Vibrio parahaemolyticus*
- Vibrio vulnificus
What does vibrio cholerae cause?
Gastroenteritis and bacteremia
What does vibrio parahaemolyticus cause?
Gastroenteritis, bacteremia and wound infections
What does vibrio vulnificus cause?
Bacteremia and wound infections
What are the characteristics of Vibrio spp. bacteria?
- Gram negative
- Facultative anaerobes
What living conditions can Vibrio spp. bacteria survive under?
They can live…
- Freely in water
- Under a broad temperature range
- Under a wide range of pH
Although they are able to survive in a wide range of pH, what is important to know about this?
They actually are susceptible to the low pH in the stomach, so you need a large dose of the bacteria (10^9) in order for enough to survive the stomach in order to cause disease in the small intestine
What is one thing that Vibrio spp. REQUIRE in order to live and grow?
Sodium chloride (NaCl)
What disease does Vibrio cholerae cause?
Cholera
- Can range anywhere from asymptomatic to severe watery diarrhea
How long is the incubation period for vibrio cholerae?
2-3 days
How long will symptoms of Vibrio cholerae last?
Up to 7 days
What percent of affected individuals will develop severe symptoms?
5-25% of infected individuals will develop SEVERE watery diarrhea
What are the symptoms of this severe case?
- Abrupt onset
- A LOT of water… Gallons per day of diarrhea
- “Rice water” stool
Can cholera be fatal?
Yes the severe dehydrationn can kill within hours
How does Vibrio cholerae spread?
Easily spreads through contaminated water
Example: the Broad street pump in London in 1854
Is cholerae a world-wide infection?
Yes… It is an important cause of diarrheal disease in the developing world
Is there any long-term immunity associated with infection?
Yes - this appears to be O antigen specific immunity
What are cholera outbreaks typically associated with?
- Natural disaster
- Population displacement
- Poor sanitary conditions
How many cholera pandemics have there been?
7 documented pandemics… We are still currently in the 7th
What are the “biotypes” of the cholera toxins that have caused the 7 pandemics?
- Pandemics 1-6 were all caused by the classic biotype
- The current pandemic (7) is caused by the “El Tor” biotype
What are the different biotypes of cholera toxins named after?
The type of O1 cholera toxin they produce
What are the features of the current El Tor biotype cholera toxin?
- It is LESS severe than the classic biotype
- Longer duration of carrying the disease compared to the classic biotype
- El Tor survives better in the environment
How many affected individuals with the El Tor biotype show severe symptoms?
Not very many…
- 1 severe case for every 30-100 severe cases
- Many less affected individuals show severe symptoms compared to the classic biotype
What happened to the El Tor biotype in 1992?
It acquired a new O antigen, becoming serotype O139 and caused a major epidemic that spread through India and other endemic countries for a decade
What is the pathogenesis of vibrio cholerae?
The toxin is co-regulated by a pilus (“bridge”) for adhering to intestinal epithelial cells
What kind of toxin is the cholera toxin?
An AB toxin
What does the toxin do once it is inside the host cell and active?
- Activates adenylate cyclase
- Increases cAMP
- Causes a massive efflux of watery secretions
Does the cholera toxin cause cell damage?
No
What type of bacterial toxin is the cholera toxin very similar to?
The ETEC LT toxin (traveler’s diarrhea)
It is very similar in structure and function
How is the cholera AB toxin encoded in the bacteria?
On a prophage
A prophage is a bacteriophage (often shortened to “phage”) genome inserted and integrated into the circular bacterial DNA chromosome or existing as an extrachromosomal plasmid
How do you diagnose vibrio cholerae?
Culture
- Use a differential media
- This would only be done in places where cholera is not common
How do you treat vibrio cholerae?
Rehydration therapy - IV and oral
- This is very important to prevent fatality from diarrhea
- Without rehydration therapy, mortality rate can be as high as 90%
What type of a bacteria is Vibrio parahaemolyticus?
Another Vibrio spp. bacteria, but this one is INFLAMMATORY
What type of disease does Vibrio parahaemolyticus cause?
- Explosive watery diarrhea
- Nausea
- Vomiting
- Abdominal cramps
- Low grade fever
What virulence factor does Vibrio parahaemolyticus have?
Kanagawa hemolysin
This induces chloride secretion thus causes watery diarrhea
What is Vibrio parahaemolyticus most commonly associated with?
The consumption of raw shellfish
Vibrio parahaemolyticus is the most common cause of two widespread illnesses. What are they?
- Bacterial gastroenteritis in Japan and Southeast Asia
- Seafood associated gastroenteritis in the US (Alabama, Mississippi, Florida, etc.)
How do you treat Vibrio parahaemolyticus?
It is self-limiting, so no intervention is necessary
How do you prevent Vibrio parahaemolyticus?
Proper cooking of shellfish
What is Yersinia enterocolitica?
- An inflammatory bacteria
- Gram negative coccobacilli
- The is related to the causative agent of the bubonic plague
Is Yersinia enterocolitica common or rare?
Common
- Widespread in nature and animals
Are most isolates of Yersinia enterocolitica virulent or avirulent?
Avirulent
How does Yersinia enterocolitica spread’?
By the ingestion of contaminated water or food
Example: improperly cooked pork
What are the symptoms of Yersinia enterocolitica?
- Fever
- Abdominal cramps
- Watery, bloody diarrhea
How long will the symptoms of Yersinia enterocolitica last?
1-2 weeks
Describe the pathogenesis of Yersinia enterocolitica
Poorly understood
- It appears as if Yersinia enterocolitica binds to and invades M-cells in the terminal ileum (similar to salmonella spp.), but by a different mechansim
Does the Yersinia enterocolitica involve T3SS?
Yes, it involves T3SS and the injection of “Yops” which stands for Yersina outer proteins
Is the toxin of Yersinia enterocolitica heat stable or heat liable?
Heat stable enterotoxin
How do you diagnose Yersinia enterocolitica?
Culture of stool
How do you treat Yersinia enterocolitica?
Supportive therapy
- It is usually self-limiting
Now we are moving on to pathogens of the LARGE intestine…
Just an FYI
What type of bacteria is colostridium difficile?
An inflammatory bacteria
- Gram positive
- Anaerobe
- Non-invasive
- Spore forming ***
Why is it relevant that c. diff can form spores?
It is very important for the c. diff life cycle
Where are we seeing c. diff emerge?
Hospitals
- HAI: hospital acquired infection
- Non-socomial (a disease originating in the hospital)
Are the diseases and symptoms that arise from c. diff always the same?
NO… Diseases and symptoms will vary
What are the different variations you might see with c. diff?
- Asymptomatic carrier
- CDAD (c. diff associated diarrhea)
- Psuedomembrane colitis
- Fulminant colitis with toxic megacolon
Describe what happens as c. diff grows
- As it grows, it can lead to toxins that cause necrosis (toxic megacolon) and a very severe thickening of the colon wall
- This may become so severe that a colon resection may be necessary
What symptoms would you see with CDAD?
C diff associated diarrhea
- Watery diarrhea
- Fecal leukocytes
- Blood sometimes
- Nausea
- Anorexia
- Fever
- Malaise
- Dehydration
- Abdominal distention and tenderness *
What symptoms would you see with pseudomembrane colitis?
- More severe watery diarrhea
- More severe general symptoms
- More severe abdominal distention and tenderness
- Yellow plaques on abdominal wall*
What symptoms would you see with fulminant colitis?
- Severe watery diarrhea
- Lethargy, fever, tachycardia
- Sudden, severe abdominal pain
- May need surgical consult
What is the pathogenesis of c. diff in the large intestine?
- AB toxin
- Cause damage to mucosa by disrupting the host cell cytoskeleton
- Causes diarrhea
How do you diagnose c. dff?
- Toxin detection in stool
- A culture is not helpful because it is part of the normal microbiota
How do you treat c. diff?
Oral vancomycin or metronidazole
How do you prevent c. diff?
Fecal transplant to prevent re-infection
What are the epidemiological factors of c diff?
- Hospitalized patients mainly
- Being treated with broad spectrum antibiotics ***
- Post-op infection or preventative surgical procedure
Describe an EHEC (E coli) infection in the large intestines
An inflammatory infection
- Enterohemorrhagic
- Gram negative
- Facultative anaerobe
Why has EHEC of the large intestine gotten a lot of news covereage?
Its serotype O157:H7 is known as the “hamburger microbe” because it can easily manifest itself in animal reservoirs such as cattle
Is EHEC an invasive microbe in the large intestine?
No, generally non-invasive
What is the epidemiology of EHEC?
- Sporadic cases and outbreaks mainly in the developed world
- Mostly associated with hamburger and vegetables that have been washed with water from rivers/streams
What disease does EHEC cause in the large intestine?
Hemorrhagic colitis
- Bloody diarrhea
- No fever
- Abdominal tenderness
What sequalae does EHEC of the large intestine lead to?
Hemolytic uremic syndrome (HUS)
- Anemia
- Kidney failure
What is the pathogenesis of EHEC of the large intestine?
- EHEC can attach to the wall of the large intestine and carry out a process similar to EPEC - “attaching and effacing”
What toxin is at play in the pathogenesis of EHEC?
Shiga-like toxin (verotoxin)
Why is it named the verotoxin?
Because it was originally discovered to kill vero cells
What does the verotoxin do exactly?
Blocks translation by cleaving part of the 60 S subunit of the ribosome
How does the Shiga-like toxin (verotoxin) travel through the body?
Through the blood
How does the Shiga-like toxin (verotoxin) cause kidney failure?
- It binds to the glomerulirich in the glycolipid receptor Gb3
- It damages the cell and causes kidney cell death and ischemic damage
- This results in kidney failure
How do you diagnose EHEC in the large intestine?
Clinical symptoms are distinct
- Bloody diarrhea WITHOUT fever
Other options
- Culture
- PCT (NAAT) detection of genes that encode the toxin
- Rapid test kits have also been developed due to recent outbreaks
How do you treat EHEC of the large intestine?
Supportive therapy
Why wouldn’t you use antibiotic therapy in EHEC of the large intestine?
Because when treated with antibiotics, the toxic part of the microbe (a bacteriophge) can sense that “the ship is going down” so it will begin to replicate in preparation for lysing itself out of the cell
This process allows EHEC to become MORE toxic to individuals
How do you prevent EHEC in the large intestine?
Properly cooking hamburger and cooking raw vegetables
What is shigella spp. of the large intestine
An inflammatory bacteria that causes many “day care center” outbreaks each year
What are the characteristics of shigella spp?
- Gram negative
- Rods
- Facultative anaerobe
- Intracellular pathogens
- Dysentery
How many cases do we see each year world wide?
150 million
600,000 deaths
Can shigell spp infect humans, animals or both?
HUMANS ONLY
How do you transmit shigella spp.?
Fecal oral route
Makes sense because it is the “day care center” disease
Does shigella have a high or low infectious dose?
Very low infectious dose
Less than 10 organims
This means that you barely need any bacteria in order to become infected
What is the incidence of shigella directly related to?
Hygiene
- Poor sanitary infrastructure
- Crowded healthcare system
- Day care centers
There are three different serotypes that we see globally. What are they?
S. soneli
S. flexneri
S. dysentariae
What types of countries do we see S. sonelii in?
Developed countries
What types of countries do we see S. flexneri in?
Developing countries
What types of countries do we see S. dysentariae in?
Underdeveloped trobical areas
This causes the most severe infections due to high Shiga toxin production
How many days after ingestion do you typically see symptoms?
1-3 days
How long does the disease last?
Self-limiting… 2 to 5 days after manifestation
Are the symptoms generalized or strain specific?
Strain specific
What are the specific symptoms of S. sonneii?
Developed countries
- Fever
- Malaise
- Watery diarrhea
Note that it can progress to more severe symptoms
What are the specific symptoms of S. flexerni and S. dysenteriae?
- Fever, malaise, watery diarrhea
- Abdominal cramps
- Tenesmus (frequently feeling need to defecate)
- Bloody, pus filled stools
HIGHLY inflammatory
Which strain has a potential for hemolytic uremic syndrome?
S. Dysenteriae
What is the pathogenesis of Shigella spp.?
- Acid resistant
- Adheres selectively to M cells and passes through them
- Undergo phagocytosis by macrophages
- Rapidly escape from the phagosomes
- Rapidly induce macrophage apoptosis
Once Shigella spp. is escapes from the phagosome, what does it do?
- Interacts with the baso-lateral face of enterocytes and induces its own uptake via T3SS
What does its T3SS do?
Injection of Ipa proteins and causes cytoskeletal rearrangement
What happens after the cytoskeletal rearrangement?
Lysis of the endocytic vacuole and spread to neighboring cells via actin polymerization at a pole
How does Shigella spread to neighboring cells?
- Hijacking of the host actin
- Evasion of host defenses
What does this spread lead to?
Ulcers form from the infected areas and diarrhea results from the severe inflammation
How do you diagnose Shigella spp?
- Stool culture using a selective media
- Serological tests to confirm the species
How do you treat Shigella?
- Rehydration
- Antibiotics (possibly)
What will antibiotics do to disease caused by Shigella?
- Shorten the duration of the illness
- Limit the disease severity
Are there any resistances to be aware of?
Ampicillin resistance is common
How will you choose an antibiotic?
It will depend on the susceptibility profile of the strain of shigella
How do you prevent Shigella?
- No vaccine
- Improving personal hygiene and sanitation
If you have an infection from Shigella, will you have long-term immunity?
NO - infection does NOT confer immunity
How commonly will you see Enteroinvasive E coli in the large intestine?
Very uncommon
What type of infection will you see?
Same as Shigella, except no shiga-toxin
Is Enteroinvasive E coli inflammatory or non-inflammatory?
Inflammatory
How is it thought that Enteroinvasive E coli obtained its pathogenicity island?
From a hotizontal gene transfer from Shigella spp.
They are very similar
A 3 yr old male presents to the emergency room with of diarrhea, fever and chills. A stool sample was cultured and grew Gram-negative rods that produce white colonies on MacConkey agar and are negative for hydrogen sulfite production. Which of the following is the most likely bacteria responsible for this patients disease?
Shigella sonneii
Maybe he goes to day care, where he could contract it
Its not campy because it is not grown under these conditions, there would be no bloody stools
A 3 yr old female patient presents to the emergency room with complaints of malaise, abdominal cramps and bloody diarrhea. Her parents are worried about her consuming rare hamburgers that they think may be associated with a recent food recall. A rapid diagnostic test of the patients stool sample tests positive for enterohemorrhagic E. coli O157:H7. What is the mechanism of action of the toxin that could cause potentially fatal sequelae are you most likely to be worried about this patient developing?
Blocking translation by cleaving a subunit of the 60S ribosome
To add that last needed piece to their application to DMU, a 22-year-old college student with a extreme aversion to seafood, participated in a service trip to Haiti. This trip was focused on providing much needed care to people still living in temporary camps after being displaced from their home after the most recent earthquake. Several days after arriving and indulging in the local cuisine provided by street vendors, the student developed a mild case of watery diarrhea. What is the most likely cause of this persons diarrhea?
Toxin production leading the efflux of electrolytes and water
