ICL 2.21: Shigella & Listeria Flashcards
what’s the microbiology of listeria?
gram (+) rod
what is the microbiology of shigella?
gram (-) rod
what pathogen caused this?
infant V., a 22-month-old girl living in Texas, became febrile, lost her appetite, and developed watery diarrhea
by the next day, her diarrhea had abated, but her parents noticed that her stools contained mucus and were blood-tinged
the number of stools and the bloody appearance increased, and the baby began to vomit. The parents brought her to a hospital emergency room. Temperature was 40 C. Shortly after arrival, she had a generalized seizure.
PE revealed a sick-looking, somnolent infant with mild dehydration and hyperactive bowel sounds.
laboratory results showed leukocytosis and a mild decrease in serum sodium and glucose.
child was given fluids and antibiotics and was fine after a few days
shigella flexneri
what does shigella cause?
bloody diarrhea and dysentery
they invade and damage the mucosa leading to bloody diarrhea
these infections are serious and life threatening
antibiotics are often required; rehydration therapy has little impact
they’re a problem in developing countries.
what is dysentery?
dysentery is characterized by frequent passage of stools (~30 per day) that typically contain small amounts of blood, mucus and pus
what are the symptoms of a shigella infection?
- dysentery = 30 stools a day containing blood, mucus and pus
- cramps
- pain from straining to pass stools
which bacteria often causes dysentery?
shigella
entamoeba histolytica can also cause it
which shigella species are most common among which populations?
S. dysenteriae and S. flexneri, associated with poverty and poor hygiene, are the predominant species in resource limited settings
S. sonnei is more common in affluent regions
what are the 4 shigella species? how are they distinguished?
- S. dysenteriae = serogroup A (the most serious*)
- S. flexneri = serogroup B
- S. boydii = serogroup C
- S. sonnei = serogroup D (least serious)
shigella is a pathotype of which other bacteria?
E. coli
Shigella is an invasive form of E. coli resulting from a large plasmid and other imported genes
all Shigella and EIEC have pINV which is a large plasmid
is the connection between E. coli and Shigella divergent or convergent?
divergent
divergent evolution refers to a single genetic population yielding distinct subpopulations
so ancestral e. coli yielded EIEC and Shigella
however, E. coli –> shigella has happened more than once
so that means shigella consists of at least 2 distantly related subclades implying that the subclades evolved into a single clade via convergence
how is shigella transmitted?
direct person-person contact
sometimes transmitted through food and water
most major outbreaks can be traced to polluted water supplies in areas with high concentrations of people like cities, refugee camps, etc.
what population is more likely to get shigella infection?
children under 5 are 10x more likely to get the disease
can shigella tolerate acid?
yes; they’re acid-resistant
this allows them to pass through the stomach without much cell death
it also explains why a small dose can cause disease
once they reach the small bowel (neutral-to-alkaline pH) they begin to grow and invade
where do shigella replicate?
once they reach the small bowel (neutral-to-alkaline pH) they begin to grow and invade
in the colon bacterial multiplication occurs within intestinal epithelial cells
how does shigella enter cells?
shigella approaches the mucosal surface via diffusion (nonmotile)
intestinal epithelial cells are resistant to invasion on their lumenal surface, but susceptible on their basolateral surfaces
so isntead there are microfold (M) cells that are adjacent with enterocytes –> the M cell binds bacteria; the lack of a brush border facilitates this binding
several pInv plasmid genes are required for M cell invasion
how does shigella spread?
shigella pass through the M cell and is released into the lamina propria while others are ingested by macrophages
macrophages start an inflammatory response and release IL-1 and IL-8
the bacteria are now near the basal surface of the epithelial cells, where their invasin binds α5β1 integrin
the inflammatory response loosens the tight junctions, allowing Shigella to penetrate
the Shigella invasin is what induces phagocytosis since epithelial cells are not professional phagocytes
Shigella also produces a “hemolysin” that lyses the phagosome, releasing bacteria into the cytoplasm
Shigella then use actin-based motility to spread into adjacent cells
what damage does shigella do to the body?
an ulcer is formed when a sufficient number of epithelial cells are invaded and slough off
neutrophils that accumulate in large numbers in the mucosa are shed in the stool where they are visible by light microscopy
bloody and pus-containing stools, and bowel pain (tenesmus), are characteristic of dysentery
does shigella cause bacteremia?
it’s uncommon except for S. dysenteriae type 1
S. dysenteriae type 1 produces Shiga toxin = ~10% risk of HUS
what is a common symptom of shigellosis?
in up to 40% of children with severe shigellosis, neurological symptoms are seen
- febrile seizures
- confusion
- lethargy
- headache
- nuchal rigidity
what kind of stools are seen with dysentery?
low volume but with blood and mucus
may or may not see WBCs
happens in the ileum and colon
there is fever, severe pain and tissue invasion involved
which type of acute infectious diarrhea does shigella cause?
dysentery
what is shiga toxin?
a cytotoxin that kills intestinal epithelial and endothelial cells
destruction of endothelial cells contributes to the bloody diarrhea
it irreversibly inactivates the mammalian 60S ribosome, halting protein synthesis
it also targets the villus cells causing decreased Na+ adsorption and excess water in the lumen
inactivation of Shiga toxin gene decreases the severity of the disease (monkeys)
how do you diagnose shigella?
shigella should be considered when a patient has bloody diarrhea or dysentery
leukocytes in the stool is diagnostic of an invasive pathogen
but to diagnose shigellosis specifically, Shigella must be cultured
however, Shigella die rapidly in the feces so samples must be fresh and processed rapidly
PCR methods are being developed to identify it
how do you treat Shigella?
FQs are the most effective but contraindicated in kids under 17
new B-lactams and cephalosporins are also effective
antibiotics reduce the severity, duration and infectivity of the disease but Shigella develop antibiotic resistance rapidly
dehydration is usually not a problem, so I.V. fluids are rarely needed
FLASHCARD: shigella
gram (-) acid resistant
4 major serotypes; A is the most serious
closely related to E. coli, especially EIEC
shiga toxin damages rRNA
causes dysentery
vacterial pathogens can undergo convergent and divergent evolution
selection for survival, growth and/or spread in different environments can result in divergence from parental strain
ex. EHEC/commensal E. coli and Shigella/EIEC diverged from one another
which pathogen caused this?
64 yr women has 5 day history of fever, headache, confusion
recent history of diarrhea which resolved before current symtpoms appeared
unable to answer simple questions, agitated, no nuchal rigidity, no focal neurological deficit
high WBC, elevated %PMNs, low Hct
normal head CT, MRI shows meningeal enhancement
CSF has WBCs but no bacteria
culture grew gram + rods
listeria monocytogenes
which pathogen causes bacterial meningitis in 0-4 weeks old and people older than 50?
listeria monocytogenes
what are PPIs and what do they do?
PPI = proton pump inhibitor
PPIs increase susceptibility to listeria infections!!
severe hypochlorhydria generated by PPI use leads to bacterial colonisation and increase susceptibility to enteric bacterial infections
also increase susceptibility to salmonella, vibrio cholerae, invasive E. coli, and vegetative C. diff
what diseases can listeria monocytogenes cause?
- listeriosis
2. intrauterine or cervical infections in pregnant women
what is listeriosis?
caused by listeria monocytogenes
invasion of intestinal epithelium then spread via growth inside macrophages
can cause septicemia, meningitis and/or encephalitis, pneumonia, corneal ulcers
7-10 days fever, myalgia, vomiting, diarrhea
what are the intrauterine/cervical infections in pregnant women from listeria monocytogenes?
can cross endothelial layer of placenta and cause spontaneous abortion or still birth
or there can be granulomatosis infantiseptica = pyogenic granulomas distributed over the infant’s body
80% perinatal/neonatal mortality
describe the motility of listeria?
actin based motility
what is the lifestyle of listeria vs. shigella?
LISTERIA
1. InIA invasin induces target cell to take up bacterium
- hemolysin HlyA disrupts phagosomal membrane
- bacteria grow in cytoplasm, move on ActA actin tails and infect adjacent cells
- released or incoming bacteria use FbpA adhesin to attach to target cell
then this cycle just starts over
SHIGELLA
literally the same thing except:
- IpaD
- IpaB
- IcsA
- IcsB
none of these proteins are related to one another
what is convergent evolution?
convergent evolution refers to distinct genetic populations coming to resemble one another
bacteria infecting a given site all face the same host defenses, and have often independently developed similar evasion or subversion strategies
ex. gram +s and gram-s converged to listeria and shigella/EIEC
how does listeria evade the immune system?
there is N-deacetylation of the PG so it’s no longer recognized by TLR2
pdgA is the enzyme responsible for this
how do you diagnose listeria?
- microscopy will show short, gram + rods; sometimes in chains
- culturing
- cell properties = motile at room temperature, weakly hemolytic
what are the culturing conditions that listeria grows in?
wide temperature range; gows at 4 C
grows in high salt
grows over a wide pH range (but not as acid resistant as shigella)
aka these are basically the conditions most often used in food preservation!
what other part of the body can listeria infect?
the heart
cardiac infections caused by L. monocytogenes represent a significant but poorly studied facet of listeriosis
subpopulations of L. monocytogenes have acquired an enhanced ability to target and invade the myocardium
where is listeria found in nature?
- soil and water
- vegetation
- variety of animals
how do you get listeria infections?
usually acquired by food poisoning
what are the risk factors for listeria infection?
- age extremes = babies and elderly
- pregnancy
- immunosuppression
how do you treat listeria?
synergistic combination therapy = B-lactam (amoxicillin) with an aminoglycoside (gentamicin)
a person in a higher-risk category
(pregnant woman, older adults, and
people with weakened immune systems)
who experiences fever and other non-specific symptoms, such as fatigue and aches, within 2 months of eating contaminated food should seek medical care and tell the physician or health care provider about eating the contaminated food
how do you prevent listeria infection?
at-risk patients should avoid raw or partially-cooked:
- milk and soft cheeses
- processed meats
- raw vegetables
is there antibiotic resistance with listeria?
it’s seen but it’s pretty rare
a small fraction show antibiotic resistance to tetracycline, clindamycin, and trimethoprim
FLASHCARD: listeria in general
listeria is a serious Gram+ human pathogen
causes variety of diseases, including meningitis
like Shigella, uses an invasin, escapes phagosome, moves between cells via actin polymerization
unlike Shigella, is sensitive to low pH
most often spread via contaminated food (grows @ 4°C)
bacterial pathogens can undergo convergent and divergent evolution
selection for survival, growth and/or spread in different environments can result in convergence with species already in a given niche
example: Shigella/EIEC and Listeria converged with one another
FLASHCARD: micro, path, epidemiology, clinical, diagnosis and treatment of listeria monocytogenes
MICROBIOLOGY: Gram-positive rod (differs from Bacillus in that Listeria does NOT form endospores), motile via flagella at room temp (at 37°C only motile via actin polym).
PATHOLOGY: Invades intestinal epithelium, grows in macrophages, can spread among cells via actin polymerization, deacetylates its peptidoglycan.
EPIDEMIOLOGY: A leading cause of neonatal meningitis (age 0-4 weeks), more common in those >50y old. Not acid resistant, so use of PPIs is a risk factor, as is immunosuppression and pregnancy.
Environmental pathogen, most commonly spread via raw produce, or dairy and meat products. Grows under conditions normally used to preserve food (4°C, high salt, mildly acidic conditions).
CLINICAL: Invasive pathogen
septicemia, meningitis/encephalitis, pneumonia, corneal ulcers
can cross placenta, leading to spontaneous abortion or granulomatosis infantiseptica
DIAGNOSIS: Culturing
TREATMENT: Antibiotic resistance appearing but still relatively rare; treatment usually synergistic combination of aminoglycoside (like gentamicin) and b-lactam (often amoxicillin)
FLASHCARD: micro, path, epidemiology, clinical, diagnosis and treatment of shigella
MICROBIOLOGY: Gram-negative enteric rod, very closely related to E. coli (especially Entero-Invasive, or EIEC)
PATHOLOGY: Causes dysentery; serotype A (S. dysenteriae) produces Shiga toxin, which kills host cells by removing same rRNA base as does the plant toxin ricin. Can spread among cells via actin polymerization.
EPIDEMIOLOGY: Outbreaks particularly common among concentrations of young children (e.g., daycare centers) due to limited handwashing; low infectious dose as Shigella species are acid resistant
CLINICAL: Depends on serotype: Serotype A causes most damage, in part due to production of Shiga toxin and bacteremia. Can lead to hemolytic-uremic syndrome (HUS) with kidney failure. All four (A-D) cause dysentery, with intestinal ulcers
DIAGNOSIS: Blood, mucus and pus in the low-volume, frequent stools. Tenesmus (bowel pain). In severe cases, neurological symptoms in ~~half of cases (febrile seizures, confusion, etc.). Confirmation requires culturing, which requires fresh samples.
TREATMENT: Antibiotics essential (hydration not usually a problem). Resistance is widespread and changing, but in general fluoroquinolones (if patient >17y old), or newer b-lactams. [Vax candidates in trials, but none yet approved.]
