ICL 2.19: EPEC, EHEC & Salmonella Flashcards

1
Q

what’s the microbiology of shigella?

A

gram (-) rod

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2
Q

what’s the microbiology of salmonella?

A

gram (-) rod

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3
Q

which bacteria are enterobacteriaceae?

A
  1. Escherichia
  2. Shigella
  3. Salmonella
  4. Klebsiella
  5. Proteus
  6. Yersinia
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4
Q

what are the major serotyping agents of all enterobacteriacea?

A
  1. H = flagella (hair)
  2. K = capsule
  3. O = LPS
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5
Q

which enterobacteriacea are enterobacteriacea that do NOT cause GI infections?

A
  1. K1 E. coli
  2. UPEC
  3. proteus
  4. klebsiella
  5. yersinia pestis
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6
Q

which enterobacteriacea are enterobacteriacea that DO cause GI infections?

A
  1. yersinia enterocolitica
  2. EPEC
  3. EHEC
  4. Salmonella

shigella also causes GI infections but it is NOT an enterobacteriacea

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7
Q

what is the purpose of diarrhea?

A

it facilitates spread of the bacterium

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8
Q

what are some of the long-term sequelae associated with diarrhea?

A
  1. HUS with renal failure following STEC/EHEC infection
  2. Guillain-Barré syndrome following C. jejuni infection
  3. malnutrition following infection with EAEC, Cryptosporidium species, or perhaps other enteric infections
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9
Q

what are the 3 clinical types of acute infectious diarrhea?

A
  1. secretory diarrhea
  2. hemorrhagic colitis
  3. dysentery
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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

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11
Q

which bacteria cause secretory diarrhea?

A
  1. vibrio cholerae
  2. EAEC
  3. ETEC
  4. EPEC
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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

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13
Q

which bacteria cause hemorrhagic colitis?

A

EHEC

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14
Q

what is dysentery diarrhea?

A

low volume, blood, mucus stool;
+/± WBCs

site = ileum, colon

there IS fever, severe pain and tissue invasion

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15
Q

which bacteria cause dysentery diarrhea?

A
  1. campylobacter
  2. salmonella
  3. shigella
  4. EIEC
  5. yersinia enterocolitica
  6. yersinia pseudoTB
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16
Q

what does EPEC stand for?

A

enteropathogenic E. coli

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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

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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.

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19
Q

how do you differentiate between different types of E. coli?

A

distinguished by serotypes:

O = LPS

H = flagellin

K = capsule

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20
Q

what does E. coli ferment?

A

ferments lactose

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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

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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

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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

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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

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25
Q

what kind of diarrhea, epidemiology, invasion, toxins and adhesins does EHEC have?

A

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

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26
Q

what population does EPEC effect?

A

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

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27
Q

how does EPEC cause diarrhea?

A

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

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28
Q

why is EPEC sometimes not reported in lab findings?

A

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

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29
Q

what is the definition of diarrhea?

A

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

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30
Q

what are the subcellular alterations that lead to diarrhea during EPEC bacterial pathogenesis?

A

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

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31
Q

what are the indications of secretory diarrhea vs. inflammatory diarrhea?

A

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

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32
Q

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

A

EHEC = entero-hemorrhagic diarrhea

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33
Q

what kind of diarrhea does EHEC cause?

A

a nonfebrile bloody diarrhea called hemorrhagic colitis

34
Q

what’s the most common serotype of EHEC?

A

O157:H7

35
Q

what does EHEC ferment?

A

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
Q

how lethal is EHEC?

A

low ID50 (50-100)

acid resistant

37
Q

which diseases is EHEC associated with?

A
  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
Q

what toxin does EHEC produce?

A

it produces exotoxin related to Shiga toxin

STEC = Shiga-toxigenic E. coli

39
Q

what is the progression of an EHEC infection?

A
  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

  1. if the toxins and bacterial LPS enter the bloodstream, the can cause an increase in cytokines and chemokines
  2. 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
Q

where is HUS most common in the US?

A
  1. CA

2. TX

41
Q

where can you find EHEC?

A
  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
Q

how serious is HUS?

A

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
Q

what is the pentad of symptoms of HUS?

A
  1. fever
  2. thrombocytopenia
  3. hemolytic anemia with schistocytes
  4. acute renal failure
  5. variable CNS symptoms
44
Q

how do you treat HUS?

A
  1. supportive care with blood transfusion
  2. control of electrolyte and water imbalances
  3. dialysis
45
Q

where does EHEC grow in the body?

A

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
Q

how does EHEC attach to cells?

A

it produces attaching and effacing lesion proteins similar to EPEC which cause a lesion similar to EPEC

47
Q

how does EHEC damage cells?

A

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
Q

how do you treat EHEC?

A

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
Q

how do you prevent EHEC infections?

A
  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
Q

why is EHEC potentially so lethal?

A

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
Q

what does EAHEC stand for?

A

entero-aggregative-hemorrhagic Escherichia coli

52
Q

what is EAHEC?

A

EAHEC = entero-aggregative-hemorrhagic Escherichia coli

it’s EAEC pAA plasmid + EHEC Stx phage = EAHEC

53
Q

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

A

salmonella typhi

aka typhoid fever!

54
Q

what are the 3 clinical syndromes associated with salmonella?

A
  1. gastroenteritis
  2. infections of particular organ systems
  3. typhoid fever
55
Q

which bacteria causes salmonella gastroenteritis?

A

S. enterica nontyphoidal serovars

primarily Enteritidis and Typhimurium

56
Q

what are the symptoms of salmonella gastroenteritis?

A
  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
Q

which organ systems does salmonella effect?

A

asymptomatic colonization of gallbladder or lower GI (carrier state)

osteomyelitis in sickle cell anemia patients

58
Q

which bacteria causes typhoid fever?

A
  1. S. typhi
  2. S. paratyphi A and B

can damage lungs, liver, spleen and/or nervous system

59
Q

where is S. enterica enterica found?

A

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
Q

how is typhoid fever transmitted?

A

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
Q

how is salmonella transmitted?

A

95% of salmonella cases are from foodborne transmission

the major culprits are serovars Typhimurium, Enteritidis and Newport

62
Q

how infectious is salmonellae?

A

large infectious dose is required

can reduce ID50 10-200x using bicarbonate or with food, where 50,000 may be sufficient

63
Q

does salmonellae survive in the stomach?

A

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
Q

is salmonellae invasive?

A

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
Q

where do salmonella multiply?

A

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
Q

which populations are susceptible to salmonella infections?

A

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
Q

what are the symptoms of typhoid fever?

A

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
Q

what is the cycle of infection of typhoid fever?

A
  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

  1. the other option is that the bacteria enters the gall bladder which can cause cholescystitis or a carrier state
  2. then the bacteria can re-enter the bile and go back to the intestines
69
Q

how does salmonella cause damage to cells?

A

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
Q

salmonella invasion of which organ can lead to a carrier state?

A

invasion of the gallbladder can lead to carrier state

typhoid bacteria can survive in gallstones

71
Q

which salmonella serovars cause endocarditis and vascular infection?

A

serovars Choleraesuis and Typhimurium

they both adhere well to endothelial cells

72
Q

how do you diagnose salmonella infections?

A
  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
Q

how do you treat gastroenteritis caused by salmonella?

A

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
Q

how do you treat typhoid fever?

A

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
Q

what disease does yersinia enterocolitica cause?

A

acute bacterial gastroenteritis

76
Q

how does yersinia enterocolitica cause disease?

A

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
Q

where is yersinia enterocolitica found in nature?

A

most often found in contaminated food, water

organism is also widespread in soil

78
Q

what are the unusual properties of yersinia enterocolitica?

A
  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
Q

how do you treat secretory diarrhea in general?

A

rehydration

not necessarily antibiotics

80
Q

how do you treat hemorrhagic colitis in general?

A

rehydration

not necessarily antibiotics

81
Q

how do you treat dysentery diarrhea in general?

A

no rehydration!!

YES to antibiotics!