ICL 2.18: E. Coli Flashcards
what is the microbiology of Escherichia?
gram (-) rod
what is the microbiology of Klebsiella?
gram (-) rod
what is the microbiology of proteus?
gram (-) rod
what is the microbiology of yersinia?
gram (-) rod
what is the reservoir and diseases associated with escherichia?
reservoir = ileum and colon of vertebrates
diseases = *UTI, *septicemia, *neonatal meningitis, diarrhea
what is the reservoir and diseases associated with proteus?
reservoir = colon of vertebrates, water, soil
diseases = *UTI, septicemia, pneumonia
what is the reservoir and diseases associated with Klebsiella?
reservoir = colon of vertebrates, water, sewage
diseases = Pneumonia, septicemia, opportunistic infections in immunocompromised patients
what is the reservoir and diseases associated with yersinia?
reservoir = rodents, pigs, water
diseases = *plague, bloody diarrhea, diarrhea, pseudoappendicitis, mesenteric adenitis syndrome
which bacteria are in the enterobacteriaceae family that are no in the GI tract?
- K1EC
- UPEC
- Proteus
- Klebsiella
- Yersinia pestis
what’s are antigens associated with enterobacteriaceae?
- LPS
- O antigen
- K antigen
- H antigen
- pili/fimbriae
the major antigens are used to type via serology –> O antigen: E. coli O157:H7
what is the function of LPS in enterobacteriaceae?
LPS binds to TLR4 on host cells which induces cytokines like TNF-alpha
TNF-alpha causes inflammation, fever, DIC, shock
what is the function of O antigen in enterobacteriaceae?
it’s part of LPS
what is the function of K antigen in enterobacteriaceae?
it’s the capsule!!
it blocks Ab and complement binding (serum resistance)
what is the function of H antigen in enterobacteriaceae?
it’s the flagella!!
provides motility
except Klebsiella and Yersinia
what is enterobacteriaceae phase variation?
the bacteria can change what is expressed under certain conditions
aka it can turn off/on virulence factors
what can enterobacteriaceae ferment?
glucose
are enterobacteriaceae anaerobic or aerobic?
aerobic but can be facultative anaerobic
what disease does e. coli K1 most often cause?
neonatal meningitis
which pathogen is causing this?
CJ is a 3-day-old baby boy born at term (40 weeks gestation)
Brought to ER for a fever of 101∘F and irritability
Mother states that all symptoms started 6-8 h prior to arrival @ ER
He has not been feeding well since.
The pregnancy was uneventful; delivery was vaginal without prolonged rupture of membranes.
However, she had a fever during labor, for which she was given antibiotics.
On examination, CJ had a full anterior fontanelle and increased tone in all four extremities
WBC: 19,000/µL
Differential: 60% neutrophils, 20% bands, 20% lymphocytes.
CSF: 1500 WBC /µL with 85% PMNs
Gram stain of CSF: showed Gram negative rods
E. coli K1
when are E. coli K1 infections most common?
E. coli K1 causes neonatal bacterial meningitis
it’s more common in the first month than at any other time of life
it’s rare but occurs in 15% of neonates with bacteremia
mortality has dropped a lot however survivors are still at high risk for neurologic sequelae and lifelong impairment as a result of infectious insult to developing brain
what are the risk factors that could cause neonatal bacterial meningitis?
- Low birth weight
- Pre-term birth
- Premature membrane rupture
- Traumatic delivery –> sepsis
- Fetal hypoxia
what are the common clinical signs of neonatal bacterial meningitis?
- Temperature instability (fever or hypothermia)
- Irritability or lethargy
- Poor feeding or vomiting
- Findings of a full, but not bulging, fontanelle
- normal neck flexion are common at
initial presentation
which two pathogens are common causes of neonatal meningitis?
- E. coli K1 = early onset (3-7 days)
2. Group B Strep = late onset
what are the steps that happen during E. coli infection?
(1) Mucosal colonization in nose/mouth
(2) Invasion of bloodstream
(3) Survival and multiplication causing high-level bacteremia
(4) Crossing the blood–brain barrier
(5) Invasion of the meninges and the central nervous system.
(6-9) lead to neuronal injury (10)
how does E. coli K1 get across the BBB?
it needs a high degree of bacteremia
then E. coli binds to and invades the brain micro-vascular epithelial cells through ligand-receptor interactions
then there’s host cytoskeletal rearragnements and activation of different signalling pathways
E. coli invades the cells but doesn’t grow intracellularly
this is transcellular traversal!
what is the E. coli K1 trojan horse mechanism?
E. coli binds to and invades macrophages in order to cross the blood brain barrier
what is the capsule of E. coli K1 made of?
poly-sialic acid
this helps it evade the immune system because it mimics our systems sialic acid = molecular mimicry*
it also binds factor H which blocks alternative complement pathway –> when factor H is bound to a cell it tells the immune system not to kill it!
how do you diagnose an E. coli K1 infection?
- bacterial isolation from the CSF by culture and/or visualization by Gram stain
- increased CSF WBCs (typically >1000/µL) with a predominance of neutrophils
- elevated CSF protein (>150 mg/dL in preterm and >100 mg/dL in term infants)
- decreased CSF glucose (<20 mg/dL [1.1 mmol/L] in preterm and <30 mg/dL [1.7 mmol/L] in term infants)
what CBC lab results will you see with an E. coli K1 infection?
WBC: 19,000/µL
differential: 60% neutrophils, 20% bands, 20% lymphocytes.
CSF: 1500 WBC /µL with 85% PMNs
gram stain of CSF: showed Gram negative rods
culture of CSF: grew E. coli. The E. coli was resistant only to ampicillin.
how do you treat E. coli K1 infection?
if you see gram (-) rods in CSF, consider E. coli, pseudomonas aeruginosa, and K. pneumoniae
you can then treat with:
- ampicillin (if it’s not resistant)
- cefotaxime = broad spectrum cephalosporin
- gentamicin = aminoglycoside
which two bacteria cause UTIs?
- UPEC = uropathogenic E. coli
2. proteus mirabilis
are men or women more susceptible to UTIs?
women
they have a shorter urethra and urethra is closer to anus
what are the two types of UTIs that can be caused by UPEC?
- cystitis (95%)
2. pyelonephritis (5%)
what is cystisis?
a type of UTI caused by UPEC
it’s an uncomplicated bladder infection that causes a burning sensation, frequent micturation, incomplete voiding, suprapubic pain
is commonly caused by recent sexual intercourse; this is why you’re supposed to pee after sex!
what is pyelonephritis?
a type of UTI caused by UPEC
leads to kidney infections!!! so more severe than cystitis
symptoms include chills.. high fever, nausea, arthralgia/myalgia, flank pain
untreated, it can lead to renal failure, bacteremia, septic shock
which pathogen is responsible for most community-acquired UTIs?
uropathogenic E. coli = UPEC
the other enterobacteriaceae like *staphylococcus, enterobacter, proteus and klebsiella can also cause UTIs but not as common
how does UPEC bind to cells?
several adhesins bind to surface facet cells of bladder, upper urinary tract and prevent bacteria being voided with urine
these adhesins include:
- type 1 pili
- pyelonephritis-associated pili
- Dr/AFA pili
which cells does UPEC infect?
they invade the superficial facet cells in the bladder –> you’ll see gram (-) rods inside the cells
there, they can cause apoptosis and exfoliation, exposing lower layers
the bacteria can also remain dormant inside intracellular vesicles and reactivation can launch recurrent episodes of cystitis
what are the virulence factors associated with UPEC?
- siderophores –> for acquiring Fe
- secreted toxins like alpha-hemolysin
these toxins alter host cell signaling cascades, modulate inflammatory responses and trigger apoptosis
what are the steps in the acute infection cycle of UPEC?
- attachment
- intracellular biofilm community formation
- IBC maturation
- exfoliation
- quiescent reservoir or start back at attachment
is proteus mirabilis motile?
yes
hyperflaggelated so they zoom around super quickly (you watched the video of them moving around)
they literally look like swarms on agar surface (ripples)
what role does urease play in proteus mirabilis?
proteus mirabilis has urease which breaks down urea into calcium phosphate and uric acid
this unfortunately can lead to lots of kidney stones!!!
how do you diagnose a UTI from either UPEC or proteus mirabilis?
- urine dip sticks –> detect nitrite and leukocyte esterase
- immersion culture media –> plastic rod coated with 2 culture mediate incubated for 24 hours
how do you treat a UTI from either UPEC or proteus mirabilis?
normally B-lactams like amoxicillin or cephalosporins are used but resistance is increasing
you could also use Bactrim (trimethoprim-sulfamethoxazole) but the resistance to this is also increasing
or you could use fluoroquinolone like ciprofloxacin or levofloxacin
if it’s a serious or complicated infection, aminoglcosides can be used but their toxicity profiles are concerning and they have to be given parenterally –> they achieve high renal and urine levels which is good to kill the bacteria
where is Klebsiella pneumoniae found in nature?
relatively ubiquitous in environment
found in water, soil, contaminated food, and intestinal flora
which diseases is K. pneumoniae associated with?
so the K1 serotype (capsule) is particularly pathogenic
it can cause:
- pneumonias –> particularly in alcoholics
- UTIs
- biliary tract infection –> now leading cause of liver abscesses in US
- wounds –>including rare necrotizing fasciitis
- ocular neurological problems
which disease is Klebsiella granulomatis associated with?
it can cause an STD that causes granuloma inguinale = that lesion looking thing by the testicles
surpisingly though, the lesions are painless!
this is endemic in tropical areas
what are the virulence factors associated with Klebsiella pneumoniae?
- capsule = major virulence determinant
- LPS
- adhesins
- siderophores
what is the function of the K. pneumoniae capsule?
it’s an acidic polysaccharide capsule that’s very thick
it’s antiphagocytic and inhibits activation of C3b
what is the function of the K. pneumoniae LPS?
causes sepsis
it also helps with immunological masking by blocking C1q and C3b binding
what are the symptoms of a Klebsiella pneumoniae infection?
primarily pneumonia symptoms such as:
- fever
- elevated respiration rate
- elevated WBCs
- elevated PMNs (neutrophils 72%)
- decreased p02 (68 mmHg)
- CXR shows patchy infiltrate from bronchiole inflammation; sometimes there’s even cavities due to necrosis from the abscess
what is the hallmark buzzword associated with klebsiella pneumoniae?
blood-tinged, thick sputum = “currant jelly”
what’s the microbiology of klebsiella pneumoniae? how do you grow it?
short gram (-) rods
nonmotile
lactose fermenting
urease (+)
what do you see when you grow klebsiella pneumoniae?
mucoid colonies
you’ll literally get like a white string sticking to the stick if you touch an agar that’s growing K. pneumoniae
how do you diagnose k. pneumoniae?
- symptoms
- positive CXR
- positive blood and sputum cultures
how do you treat K. pneumoniae?
- extended spectrum B-lactams = piperacillin or ticarcillin
- newer cephalosporins combined with aminoglycosides
ultimately though, antibiotic choice depends on resistance pattern
however, there’s a high mortality rate even with proper therapy
which pathogen is responsible for the black plague?
yersinia pestis
it literally killed 1/3 of europes population in the 1300s
what are the two diseases that yersinia pestis causes?
- bubonic plague (not as bad)
- pneumonic plague (you’re screwed)
both transmitted via the oriental rat flea to humans
what are the steps in the transmission of the bubonic plague?
- flea drinks rat blood that carries yersinia pestis
- bacteria multiply in the flea’s gut
- gut becomes clogged with bacteria
- flea bites human and regurgitates blood into open wound
- human is infected
where are yersinia pestis infections common in the US? the world?
4 corners
and out west in general
however in the world in general, we’re worried about Madegascar
what are the symptoms of yersinia pestis infection?
- buboes = swollen, painful lymph nodes
- necrosis secondary to DIC
so because of the DIC, circulation gets cut off to the extremities and you literally get black fingers and toes and that’s how it got its name as the black plague
what do the virulence factors of yersinia pestis do?
yersinia outer proteins (Yops):
- block phagocytosis
- block platelet activation
which cells does yersinia pestis infect?
yersinia pestis binds to APCs like langerhans and alveolar mecrophages
they do this by LPS binding to DC-SIGN/CD209 receptor
this results in delivery of the bacteria to CD4+ lymphocytes in nodes
how does LPS in yersinia pestis help with immune invasion?
the LPS switching from 6 to 4 carbon chain
when it does this, the 4 chain LPS is no longer recognized by TLR4!
this is how it evades the immune response
how does a yersinia pestis infection progress?
so for the first 36 hours, there’s no immune response! no inflammation or proinflammator cytokines are released because of the LPS switching that inhibits TLR4
however, after the first 36 hours our immune system somehow figures things out and there’s a very robust inflammatory response
how do you diagnose yersinia pestis infection?
- Y. pestis (unlike other Yersiniae) is NON-motile at all temperatures
- Wright’s stain preferentially stains granules at the ends of the bacteria (resembling a closed safety pin)
- fluorescent antibody (DFA) assay for F1 glycoprotein of capsule –> this is the key test now*
- PCR
how do you treat yersinia pestis infections?
DOC for all forms is streptomycin
however this drug is hard to get in the US because it has significant toxicity
instead, gentamicin, doxycycline, chloramphenicol are used
what is used for yersinia pestis prophylaxis?
doxycyline
FLASHCARD: E. coli K1
one of leading causes of neonatal meningitis; pre-term birth is risk factor
temp instability, irratability or lethargy, full fontanelle; often in first 3-7 days
K1 polysialic acid capsule is major virulence factor; molecular mimicry
treat with ampicillin or cephalosporins and aminoglycosides
FLASHCARD: UPEC
uropathogenic E. coli
major cause of community-acquired UTIs
uses adhesins (pili) to attach to and invade facet cells
FLASHCARD: proteus mirabilis
another cause of UTIs
swarming motility (hyperflaggelated) and urease –> kidney stone formation
check susceptibility; treat UTI with β-lactams, trimethoprim-sulfamethoxazole, or fluoroquinolone
FLASHCARD; Klebsiella pneumoniae
can cause serious pneumonia in older alcoholics; ‘currant jelly’ sputum
no flagella; major virulence factor is its thick K1 capsule
check antibiotic resistance; cephalosporins + aminoglycosides
FLASHCARD: yersinia pestis
plague; killed 1/3 of Europe in 1300s
major virulence factors include tetra-acylated lipid A, protein capsule, and type III secretion system (TTSS) with Yops
no flagella
wright stain = resembles a safety pin
direct fluorescent antibody
streptomycin (gent, doxy, chlor) treatment early
