ICL 2.19: EPEC, EHEC & Salmonella Flashcards
1
Q
what’s the microbiology of shigella?
A
gram (-) rod
2
Q
what’s the microbiology of salmonella?
A
gram (-) rod
3
Q
which bacteria are enterobacteriaceae?
A
- Escherichia
- Shigella
- Salmonella
- Klebsiella
- Proteus
- Yersinia
4
Q
what are the major serotyping agents of all enterobacteriacea?
A
- H = flagella (hair)
- K = capsule
- O = LPS
5
Q
which enterobacteriacea are enterobacteriacea that do NOT cause GI infections?
A
- K1 E. coli
- UPEC
- proteus
- klebsiella
- yersinia pestis
6
Q
which enterobacteriacea are enterobacteriacea that DO cause GI infections?
A
- yersinia enterocolitica
- EPEC
- EHEC
- Salmonella
shigella also causes GI infections but it is NOT an enterobacteriacea
7
Q
what is the purpose of diarrhea?
A
it facilitates spread of the bacterium
8
Q
what are some of the long-term sequelae associated with diarrhea?
A
- HUS with renal failure following STEC/EHEC infection
- Guillain-Barré syndrome following C. jejuni infection
- malnutrition following infection with EAEC, Cryptosporidium species, or perhaps other enteric infections
9
Q
what are the 3 clinical types of acute infectious diarrhea?
A
- secretory diarrhea
- hemorrhagic colitis
- dysentery
10
Q
what is secretory diarrhea?
A
copious, watery stools; ~no blood or WBCs
site = small intestine
there may or may not be fever and severe pain
there may or may not be tissue invasion
11
Q
which bacteria cause secretory diarrhea?
A
- vibrio cholerae
- EAEC
- ETEC
- EPEC
12
Q
what is hemorrhagic colitis?
A
copious, like liquid blood stool;
~no WBCs
site = colon
there may or may not be fever and severe pain
there may or may not be tissue invasion
13
Q
which bacteria cause hemorrhagic colitis?
A
EHEC
14
Q
what is dysentery diarrhea?
A
low volume, blood, mucus stool;
+/± WBCs
site = ileum, colon
there IS fever, severe pain and tissue invasion
15
Q
which bacteria cause dysentery diarrhea?
A
- campylobacter
- salmonella
- shigella
- EIEC
- yersinia enterocolitica
- yersinia pseudoTB
16
Q
what does EPEC stand for?
A
enteropathogenic E. coli
17
Q
which pathogen caused this?
Two weeks after his father’s bout with cholera during a trip to Peru, baby D. stopped feeding and developed watery diarrhea.
His rectal temperature was 38°C. His parents brought the infant to the pediatrician.
The baby had signs and symptoms of dehydration, with an estimated fluid loss of ~7% of body weight, and was admitted to the hospital.
Neither leukocytes nor red blood cells were seen in the stool
Baby D. was given an oral rehydration solution for several days.
His fever abated and appetite returned although the diarrhea persisted.
The preliminary laboratory report stated that the stool cultures contained “normal fecal flora.” –> two days later they were able to identify a pathogen
Baby D. improved and was discharged after 4 d, having lost 1 lb in weight. One month later, he returned to normal growth.
A
enteropathogenic E. coli = EPEC
18
Q
what is the most abundant facultative anaerobe in normal human feces?
A
escherichia coli
it’s outnumbered by strict anaerobes 1000:1
most E. coli are avirulent and live symbiotically within us.
19
Q
how do you differentiate between different types of E. coli?
A
distinguished by serotypes:
O = LPS
H = flagellin
K = capsule
20
Q
what does E. coli ferment?
A
ferments lactose
21
Q
what kind of diarrhea, epidemiology, invasion, toxins and adhesins does ETEC have?
A
ETEC = entero-toxigenic E. coli
diarrhea = water, no inflammation or fever
worldwide; usually travelers
non-invasive to other tissues
toxins = LT and ST
adhesins = fimbrial, coloniz’n, factor Ags
22
Q
what kind of diarrhea, epidemiology, invasion, toxins and adhesins does EPEC have?
A
EPEC = enter-pathogenic E. coli
diarrhea = water, usually no inflammation of fever
effects infants; under 1 year old
may or may not invade other tissues
toxins = shiga-like?
adhesins = intimin and bundle-forming pili
23
Q
what kind of diarrhea, epidemiology, invasion, toxins and adhesins does EAEC have?
A
EAEC = entero-aggregative E. coli
diarrhea = persistent; no inflammation or fever
effects infants less than 6 months old
no invasion of other tissues
toxins = EAST, pet toxin (plasmid encoded toxin)
adhesins = fimbrial, adherene, fimbriae
24
Q
what kind of diarrhea, epidemiology, invasion, toxins and adhesins does EIEC have?
A
EIEC = entero-invasive E. coli
diarrhea = dysentery, inflammation, fever, mucus and blood
super rare; often foodborne
does invade other tissues
toxins = hemolysin (HlyA)
adhesins = afimbrial, invasive, pasmid Ag
25
what kind of diarrhea, epidemiology, invasion, toxins and adhesins does EHEC have?
EHEC = entero-hemorrhagic
diarrhea = hemorrhagic colitis; intense inflammation, HUS
common in western nations
may or may not invade other tissues
toxins = shiga-like (Stx)
adhesins = intimin, bundle-forming pili
26
what population does EPEC effect?
EPEC = enteropathogenic E. coli
effects kids < 1 year old --> causes outbreaks of diarrhea in nurseries
EPEC rarely causes serious disease in older children or adults
there was one case in a food related EPEC strain causing illness in adults but that's it so it's often overlooked during investigation of food-associated illness so don't totally ignore EPEC if you hear adult or food-borne
outbreaks continue to occur in children < 5 y old in many countries, especially in nursery and hospital settings
27
how does EPEC cause diarrhea?
the diarrhea is caused by a complex mechanism that does NOT involve secreted exotoxins
the bacteria bind loosely via a fimbrial adhesin (Bfp) and then they alter actin polymerization of the microvilli forming an effacing lesion
EPEC injects host cell with Tir, which appears on membrane and serves as binding site for intimin on the bacterium
bacteria then stick very tightly via intimin (an OMP), which binds to Tir that was injected by bacteria in the first place
28
why is EPEC sometimes not reported in lab findings?
lab will sometimes not report a pathogen when they find E. coli, because they did not test specifically for a pathogenic form such as EPEC, and almost EVERYONE has E. coli in their GI tract ; it's part of the normal flora
29
what is the definition of diarrhea?
water accounts for 75% of the mass of healthy human stool
if it rises to greater than 85% coupled with increased frequency of bowel movements it's classified as diarrhea
30
what are the subcellular alterations that lead to diarrhea during EPEC bacterial pathogenesis?
membrane bound colonocyte aquaporins (AQP2 and AQP3), are re-localized to the cytoplasm during infectious diarrhea
the decrease of AQPs at enterocyte membranes might restrict water re-absorption leading to diarrhea
31
what are the indications of secretory diarrhea vs. inflammatory diarrhea?
epithelial alterations that result in an increase in secretion or decrease in absorption, coupled with a lack of structural damage to the tissue are general indications of secretory diarrhea
whereas inflammatory diarrhea usually involves damage to the mucosa
32
what pathogen caused this?
Mr. R, 85 years old was awakened by the onset of severe abdominal cramps, primarily in the lower right quadrant of the abdomen
soon had watery diarrhea every 15-30 minutes with visible blood --> later that day stools were bright red and seemed to consist mostly of blood
nauseated but did not vomit; did not have a fever but had tenderness over the colon
Mr. R was hospitalized, bloody stools continued. A barium enema revealed edema of the ascending and descending colon with spasmic areas
stool cultures were negative for Salmonella and Shigella
patient was treated with IV fluids and recovered over the next 7 days
the day before becoming ill Mr. R was visited by his 2-y-old granddaughter, and they ate some fast food burgers --> three days later, the child developed diarrhea that was tinged with blood. She began to vomit and urine output diminished
the child went to the hospital. labs showed a significant decrease in platelets and RBCs, which looked abnormal
the diagnosis was HUS
EHEC = entero-hemorrhagic diarrhea
33
what kind of diarrhea does EHEC cause?
a nonfebrile bloody diarrhea called hemorrhagic colitis
34
what's the most common serotype of EHEC?
O157:H7
35
what does EHEC ferment?
most are sorbitol-NONfermenting
so sorbitol is a cheap and rapid screen, but it doesn’t pick up all EHEC strains since there's a couple that do ferment sorbitol
36
how lethal is EHEC?
low ID50 (50-100)
acid resistant
37
which diseases is EHEC associated with?
1. HUS --> EHEC is responsible for 90% of HUS cases
2. most common cause of acute renal failure in children
deaths are most frequent in young shildren
38
what toxin does EHEC produce?
it produces exotoxin related to Shiga toxin
STEC = Shiga-toxigenic E. coli
39
what is the progression of an EHEC infection?
1. infest STEC-contaminated food or water
2. STEC enter the intestines and produce Stx1 and/or Stx2 and colonization factors such as intimin for LEE+ strains and other adhesins for LEE- strains
in 3 days, this will lead to diarrhea and in another 1-2 days will cause hemorrhagic collitis
3. if the toxins and bacterial LPS enter the bloodstream, the can cause an increase in cytokines and chemokines
4. toxin and bacterial LPS make it to the kidney where the toxin causes damage to the glomerular endothelial cells and the immune mediators lead to a prothrombotic state that can result in HUS
40
where is HUS most common in the US?
1. CA
| 2. TX
41
where can you find EHEC?
1. main reservoir for human infections is cattle
2. undercooked meat
3. contaminated ground water
4. unpasterized liquids
5. petting zoos
6. person to person spread
7. swimming pools
so if the cattle are infected they become hamburger meat and we get sick from that or if the cattle drink ground water and infect the ground water and then the water gets used to water our vegetables then we get infected that way too...
42
how serious is HUS?
EHEC doesn't kill a lot of people, it's unlikely to cause a major epidemic, and it's treatable
HUS on the other hand is serious and starts days or weeks after gastroenteritis caused from Shigella or EHEC
HUS is associated with damage to renal glomerular endothelium by toxins and is the #1 cause of pediatric kidney failure
43
what is the pentad of symptoms of HUS?
1. fever
2. thrombocytopenia
3. hemolytic anemia with schistocytes
4. acute renal failure
5. variable CNS symptoms
44
how do you treat HUS?
1. supportive care with blood transfusion
2. control of electrolyte and water imbalances
3. dialysis
45
where does EHEC grow in the body?
EHEC grows in the terminal regions of the colon
it's confined to the gut mucosa and multiplies locally
it does NOT invade the blood stream
46
how does EHEC attach to cells?
it produces attaching and effacing lesion proteins similar to EPEC which cause a lesion similar to EPEC
47
how does EHEC damage cells?
EHEC can damage blood vessels via shigalike toxins (Stx) or host inflammatory cytokine response
EHEC produces filaments, some of which stick into the cell surface underlying this dividing bacterium
toxic proteins may flow into the cell through these filaments
48
how do you treat EHEC?
antibiotics may be used, BUT:
they can make the disease worse by lysing the cells which would release a bolus of Shiga-like toxins and LPS
oral rehydration is usually sufficient or IV fluids
the actual challenge is treating the complications of the disease like dialysis for HUS
49
how do you prevent EHEC infections?
1. clean water supply
2. wash hands
3. proper storage and pasteurization of foods
4. vaccines exist but are not effective enough for general use
50
why is EHEC potentially so lethal?
because it can gather on the surface of an intestinal wall in a very dense pattern which possibly enhances the bacteria's ability to pump the shiga toxin into the body
51
what does EAHEC stand for?
entero-aggregative-hemorrhagic Escherichia coli
52
what is EAHEC?
EAHEC = entero-aggregative-hemorrhagic Escherichia coli
it's EAEC pAA plasmid + EHEC Stx phage = EAHEC
53
what pathogen caused this?
Ms. J., an Asian exchange student in the U.S., returned home for a 3-month visit
near the end of her visit, she cared for her aunt who had high fevers and some diarrhea
three weeks later, back in the U.S., Ms. J. had shaking chills and fever of 38.5°C, with headache, muscle pain, and loss of appetite; fever increased over the next several days
when seen at the Student Health Service, she appeared ill and confused. Her abdomen was diffusely tender. Her liver and spleen were enlarged, though she did not have jaundice
in spite of the high fever, her pulse was relatively low at 90 beats per minute. The white blood cell count was low (3000/µl), with a moderate monocytosis
treated with cephtriaxone
however, 6 weeks later all of her symptoms recurred, including a maximum fever of 38.5°C. treated with cephtriaxone again and she had a rapid response
she experienced no further recurrence
salmonella typhi
aka typhoid fever!
54
what are the 3 clinical syndromes associated with salmonella?
1. gastroenteritis
2. infections of particular organ systems
3. typhoid fever
55
which bacteria causes salmonella gastroenteritis?
S. enterica *nontyphoidal* serovars
primarily Enteritidis and Typhimurium
56
what are the symptoms of salmonella gastroenteritis?
1. nausea
2. vomiting
3. self-limiting diarrhea
similar to watery diarrheas
5% lead to bacteremia where a dangerous complication of that is infectious endarteritis = inflammation of the inner lining of an artery
57
which organ systems does salmonella effect?
asymptomatic colonization of gallbladder or lower GI (carrier state)
osteomyelitis in sickle cell anemia patients
58
which bacteria causes typhoid fever?
1. S. typhi
2. S. paratyphi A and B
can damage lungs, liver, spleen and/or nervous system
59
where is S. enterica enterica found?
in the normal flora of many animals
these strains cause gastroenteritis and are usually transmitted by chicken meat, eggs and dairy products
outbreaks are more common in summer and often related to contaminated egg or chicken salad
60
how is typhoid fever transmitted?
fecal-oral transmition
human carrier
S. Typhi is a strictly human pathogen and could theoretically be eradicated with the proper vaccine
but it can also involve contaminated food or water
61
how is salmonella transmitted?
95% of salmonella cases are from foodborne transmission
the major culprits are serovars Typhimurium, Enteritidis and Newport
62
how infectious is salmonellae?
large infectious dose is required
can reduce ID50 10-200x using bicarbonate or with food, where 50,000 may be sufficient
63
does salmonellae survive in the stomach?
yeah but they're more acid sensitive than Shigellae of EHEC
survivors from stomach travel to distal ileum and colon where they attach to and penetrate mucosal barrier
64
is salmonellae invasive?
yes!!!
survivors from stomach travel to distal ileum and colon where they attach to and penetrate mucosal barrier
to invade a cell, Salmonella causes a characteristic ruffling of the plasma membrane
they probably pass through M-cells but they may even be able to traverse tight junctions
invasin forces phagocytosis
65
where do salmonella multiply?
unlike Shigella, Salmonella do NOT remain in epithelial cells
instead they pass into the blood causing transient bacteremia; usually asymptomatic
in typhoid fever the initial bacteremia carries salmonellae to regional lymph nodes, liver where the bacteria multiple in macrophages -- the patient is still asymptomatic at this point
then when a threshold is reached, bacteria are released into the bloodstream initiating a continuous bacteremia -- this is when the clinical illness starts with daily high fevers for 4-8 weeks if untreated
66
which populations are susceptible to salmonella infections?
in healthy individuals the (nontyphoidal) bacteria are rapidly killed by phagocytes
but sickle cell anemia, AIDS, leukemia patients etc. are more susceptible to salmonellosis
67
what are the symptoms of typhoid fever?
onset of illness is insidious, with gradually increasing fatigue and a fever that increases daily from low-grade to as high as 102°F–104°F (38°C–40°C) by the third to fourth day of illness
headache, malaise, and anorexia are nearly universal
hepatosplenomegaly can often be detected
a transient, macular rash of rose-colored spots can occasionally be seen on the trunk
fever is commonly lowest in the morning, reaching a peak in late afternoon or evening
untreated, the disease can last for a month
the serious complications of typhoid fever generally occur after 2–3 weeks of illness and may include intestinal hemorrhage or perforation, which can be life threatening
68
what is the cycle of infection of typhoid fever?
1. bacteria is ingested and goes to the colon
2. then it goes to the lymphatic system
3. bacteremia; bacteria enters blood
4. bacteria spreads to liver, spleen, BM
this can lead to secondary bacteremia which causes fever, kidney and other organ infections
5. the other option is that the bacteria enters the gall bladder which can cause cholescystitis or a carrier state
6. then the bacteria can re-enter the bile and go back to the intestines
69
how does salmonella cause damage to cells?
interaction of gastroenteritis-producing salmonellae with epithelial cells activates an inflammatory response and damages intestinal mucosa
salmonella can also grow in macrophages which is critical for the virulence
70
salmonella invasion of which organ can lead to a carrier state?
invasion of the gallbladder can lead to carrier state
typhoid bacteria can survive in gallstones
71
which salmonella serovars cause endocarditis and vascular infection?
serovars Choleraesuis and Typhimurium
they both adhere well to endothelial cells
72
how do you diagnose salmonella infections?
1. growth on specific culture media = XLD agar --> salmonella can ferment the sugar xylos to produce acid which turns the agar from red to yellow
2. serology
73
how do you treat gastroenteritis caused by salmonella?
it's not always treated with antibiotics because drugs do not alter the duration of the disease
also drugs can prolong the time of carriage
74
how do you treat typhoid fever?
typhoid fever IS treated with antibiotics which reduce morbidity and mortality
FQs reduce the period of illness and eradicate the organism
however, excessive use of FQs is selecting for resistance
75
what disease does yersinia enterocolitica cause?
acute bacterial gastroenteritis
76
how does yersinia enterocolitica cause disease?
it's invasive and appears to cause disease by tissue destruction
invasion of human epithelial cells and penetration
of the mucosa occurs in the ileum, followed by multiplication in Peyer’s patches
drainage into mesenteric lymph nodes can lead to systemic infection or mesenteric adenitis
death is rare, but Y. enterocolitica bacteremia is associated with a case fatality rate of 34-50%.
77
where is yersinia enterocolitica found in nature?
most often found in contaminated food, water
organism is also widespread in soil
78
what are the unusual properties of yersinia enterocolitica?
1. inability to chelate iron; does not produce siderophores but can use those produced by other bacteria
2. ability to grow at 4°C = grows in contaminated food (or blood) even when refrigerated
3. can mimic symptoms of appendicitis
79
how do you treat secretory diarrhea in general?
rehydration
not necessarily antibiotics
80
how do you treat hemorrhagic colitis in general?
rehydration
not necessarily antibiotics
81
how do you treat dysentery diarrhea in general?
no rehydration!!
YES to antibiotics!
