Shigella, Salmonella, & Yersinia Flashcards
All species of Shigella are capable of causing what disease?
Bacillary dysentery
Note that EIEC also causes dysentery.
Of the 4 types of Shigella we learned about, which causes the most severe disease? Which are most common in the US?
S dysenteriae (type 1) causes the most severe disease.
S flexneri and S sonnei are the two that are most common in the US
What kind of medium is best for identifying Shigella? How does it appear on that medium?
XLD agar is best. The medium will retain its original rosy color, and the colonies will be clearish WITHOUT black colonies.
(E coli - yellow clearings due to lactose fermentation, no black colonies.
Salmonella - no yellow clearings, black colonies due to H2S production).
Where in the world are Shigella spp. found?
All countries
How is Shigella transmitted?
Highly communicable - LOW infectious dose!! (~ 10 organisms!)
Fecal-oral: contaminated food/water; fomites; person-to-person; insect vectors
How does Shigella invade host cells?
Shigella binds and passes into M cells of Peyer’s Patches.
M cells bring Shigella into the lamina propria, where they are engulfed by macrophages. Shigella escapes the endocytic vacuole and induces apoptosis of the macrophage.
Next, the bacteria use a Type III injection secretion system on the basolateral face of the enterocytes to inject virulence proteins. This causes remodeling of the cytoskeleton, leading to the bacteria being engulfed by the enterocyte.
Once again, they escape the endocytic vacuole of the enterocyte, and then begin to replicate in the cytoplasm, while also recruiting host actin to form “comet tails” to facilitate movement through cytoplasm into other adjacent enterocytes.
Video:
https://youtu.be/CtsQ6lZ3RI4?t=69
Shigella is able to induce apoptosis of its host enterocyte. When this happens, what is the clinical manifestation?
Mucosal ulcers.
Salmonella typhi is able to induce apoptosis of its host enterocyte. When this happens, what is the clinical manifestation?
Seeding of the bloodstream –> typhoid fever
Which Shigella spp. typically produces Stx?
S. dysenteriae type 1
You have a patient presenting with dysentery. Culture on XLD agar shows no yellow clearings or black colonies. How would you proceed?
The causative agent could be Shigella or EIEC. PCR would be best to identify the organism. If Shigella, patient should be treated with antibiotics.
Empiric antibiotics should NOT be used, since the symptoms are so close to those caused by E coli, and if the pathogen is EHEC, use of antibiotics increases the likelihood of developing HUS!
Why is it important to treat patients with Shigella-associated disease with antibiotics?
If untreated, patients with Shigella can shed asymptomatically for 6 weeks, and due to the very low infectious dose, this can cause local outbreaks.
Treatment with antibiotics also reduces the severity and duration of disease.
What is an important pathogenic characteristic of Shigella?
Acid resistance: able to survive acidic environment of the stomach. This contributes to the very low infectious dose associated with Shigella.
Describe the appearance of Shigella, E coli, and Salmonella on XLD agar.
Shigella: agar retains rose color; clearish colonies
E coli (most, not EIEC): Yellow clearings on agar; clearish colonies
Salmonella: Bright red agar; black colonies
In what animals is Shigella found?
Only humans (but can be transmitted via insect vectors)
Of the pathogens we discussed, what is a differentiating metabolic characteristic of Salmonella spp?
H2S production (seen on XLD as black colonies, or on Hektoen Enteric medium as black colonies on blue-green medium.
What are the causative agents of typhoid/enteric fever? Where are they found?
Salmonella enterica subsp. enterica, serovars Typhi and Paratyphi
Found in humans only, primarily in resource-limited countries
Salmonella enterica serovars other than Typhi and Paratyphi cause what disease? Where are they found?
Gastroenteritis. They are found in multiple animal reservoirs and occur in resource-rich countries.
What is the most common source of salmonella-associated gastroenteritis in the US?
Poultry products: chicken, eggs
Milk
Cold-blooded pets: turtles, snakes, fish
Of the forms of enteric fever, which is most severe?
S. Typhi causes a more severe disease (typhoid fever) than S. Paratyphia (paratyphoid fever, but also confusingly called typhoid fever)
In general, how are Salmonella spp. transmitted?
Fecal-oral transmission: contaminated food/water
Person-to-person transmission (likelihood varies between serovars), including via asymptomatic carriage.
Spread via animal reservoirs for serovars other than S Typhi/Paratyphi
What kind of virulence factors are used by Salmonella spp.?
O antigen: part of the lipopolycaccharide
H antigen: flagellum
Pili: similar to E coli type 1
Type III injection system
Buzzword: Ruffling of host cells
Salmonella
Generally describe Salmonella’s process of invasion in gastroenteritis
Pili help mediate attachment to mannose on intestinal mucous membrane surfaces
Type III injection secretion system injects effector proteins, which manipulate host actin, causing ruffles to form
The ruffles endocytose the bacteria, and the bacteria replicate in the endocytic vacuole (remember that Shigella escapes)
They then escape epithelial cells and spread to lamina propria and lymphatics:
- In lamina propria, get phagocytosed by macrophages and induce apoptosis –> causes inflammatory response and diarrhea
- Some strains can spread into bloodstream (S. Choleraesuis) –> bacteremia
Where does Shigella replicate?
Cytoplasm
Where does Salmonella replicate?
Endocytic vacuoles
How does the pathogenesis leading to enteric fever differ from that of gastroenteritis?
Mostly similar, with a few differences:
- Vi antigen-containing capsule: inhibits neutrophil phagocytosis
- Bacteria undergo extended replication in phagocytic cells. This causes hypertrophy of Peyer’s patches, and dissemination to spleen, liver, bone marrow. Can cause necrosis of Peyer’s patches.
- Typhoid (A-B) toxin may play a role.
Your patient became sick after contact with a jerk of a turtle. What symptoms do you expect?
Nausea Vomiting Fever Chills Abdominal pain Watery diarrhea
Very generally describe the s/s of typhoid fever:
Prolonged fever
Sustained bacteremia
Profound involvement of reticuloendothelial system (spleen, liver, bone marrow)
3 stages of disease, each about 1 week long
When is the best time to order stool culture for a patient with suspected typhoid fever?
The second week (or second 10 days) of disease:
Diarrhea becomes significantly worse, with pus and blood present
Rose spots on abdomen and chest may develop
What are the clinical manifestations of typhoid fever during the first week of illness?
Fever
Nonspecific malaise, anorexia, myalgia, and headache
Constipation or mild diarrhea
When is the best time to order blood cultures on a patient with suspected typhoid fever?
During the first week/ten days of disease.
What are Salmonella organisms doing during the first week of typhoid fever?
Penetrating the mucosa
Reaching the mesenteric lymph nodes
Spreading to the blood stream
Eventually reaching liver, spleen, bone marrow
What are Salmonella organisms doing during the second week of typhoid fever?
Infecting gallbladder Returning to the intestine via the biliary system Infecting Peyer's patches Ulcerating mucosa Increasing secretions into the GI
What are the clinical manifestations of typhoid fever during the third week of illness?
Prostration Generalized sepsis Hepatosplenomegaly Possible intestinal perforation Hopeful development of effective immunity/containment of infection
What are the clinical manifestations of Salmonella-associated gastroenteritis?
Acute diarrhea
Abdominal cramping
Fever
(Often associated with a community outbreak)
Your patient initially presents with constipation which progresses to bloody diarrhea. What is the suspected organism?
Salmonella Typhi or Paratyphi
When would a urine culture be performed on a patient with typhoid fever?
After resolution. Meant to ensure that they are no longer carrying/shedding. A stool culture should also be done at this time.
What is the treatment for Salmonella-associated gastroenteritis?
Supportive
What is the treatment for enteric fever?
Extended-spectrum cephalosporins and ciprofloxacin
What preventative measures can be taking for protecting against typhoid fever?
Vaccines exist, but only give partial protection for a few years.
Sanitary systems and hygienic practices!!
What are thee important elements of Yersinia pathogenesis?
Invasins: aid attachment by binding to integrins
Yops: injected by Type III injection secretion system
LPS: responsible for most of the systemic symptoms
How are Yersinia enterolitica and Y pseudotuberculosis transmitted?
Consumption of contaminated food
Associated with rodents and domestic animals
What cells are initially affected during Yersinia infection?
Mesenteric lymph nodes
Peyer’s patches
Buzzword: Arthritis
Yersinia (post-infectious sequelae)