Vibrio!!! MICROM442 Deck 19 Flashcards
vibrio cholera are…?
SHORT and GMN rods
vibrio cholera have a single…?
polar flagella
where do vibrio cholera grow well?
alkaline media and in
presence of bile salts (TCBS: thiosulfate citrate bile salts
sucrose agar); low tolerance for acid or drying
history of v.cholera
massive watery diarrhea, little abdominal pain, no fever
treatment v.c
rehydration
diagnosis of v.c =
history
Filippo Pacini
ahead of the game, an illness cause by “vibrions”, talented microscopist
Filippo Pacini
- Talented microscopist
- Noted severe disruption of intestinal mucosa with
millions of closely associated bacteria - Duodenal lesions continued to progress for hrs after
patient’s death
5th pandemic, vc identified as a causative agent by
Robert Koch
Robert Koch described vc as
-bacilli present only in the
mucosa of corpses of persons who died of cholera
- Isolated first pure culture: bacilli described as ‘a little
bent, like a comma’
- Able to replicate in moist cloth or damp earth
- Failed to reproduce the disease in non-human animals
- Although bacilli rare in stools during early stages of
cholera, rice-water stools were almost pure cultures
2 serotypes of VC are epidemic and they are
O139 and O1 serotypes
which serotype of vs is toxigenic?
O139
First 6 pandemics caused by
Classical” O1 serotype (O = O-antigen or LPS, 1=first
serotype)
3.2x106 bp/genome, moderate environmental survival, cases/carriers=1:2-4
7th (current) pandemic 1961 in Indonesia, caused by “El Tor” biotype
Also O1 serogroup; 2.6x106 bp/genome
much better environmental survival, cases/carriers=1:30-100
3 genomic waves in 7th pandemic
1st estimated to have emerged ~1952
3rd estimated to have emerged in 1988
O139 emerged during 2nd pandemic wave: 1992 in India
can infect adults previously infected with O1 strains
Human colonization creates a hyperinfectious bacterial state which
Underscores the role of human-to-human transmission and
rapid spread during outbreaks
No evidence of cholera between outbreaks for vc because
Bacteria enter active but not culturable [ABNC] state;
attacked by lytic vibriophages
can immunity develop after infection?
yes, infx is serogroup specific
remove contaminated water or food =
remove the epidemic
O1 and O139 able to cause epidemic based on which characteristics?
-Tcp (type IV) pilus bc needs to attack somehow
-CtxAB (cholera toxin) -> not needed but present in both
positive regulator
toxRS -> toxT -> tcp pilus (toxT also positively regulates ctxAB) -> ctxAB
filamentous phage carry?
cholera toxin genes, CTX=AB subunit toxin that catalyzes ADP RIBOSYLATION of stimulatory G-protein during cAMP production
CTXø =
6.9 kb single-stranded filamentous bacteriophage
carries critical genes involved in virulence
cp (toxin co-regulated pilus) is the
CTXø surface receptor
Bacteriophage production does not cause
bacterial lysis or
slow growth
Specific binding of CTX to glycolipid GM1, specifically in association with plasma membrane lipid rafts
(microdomains in the membrane that are rich in cholesterol), directs CTX “retrograde” transport through
what amounts to a reversal of the normal host biosynthetic pathway for secretory and membrane proteins.
- CtxB binds GM1
among lipid rafts on
plasma membrane - retrograde
transport to golgi-
ER - CtxA1 unfolds in
ER - translocated into
the cytoplasm - ADP ribosylates
stimulatory G-
protein - increased
intracellular
[cAMP] - secretion of Cl,
H2O - Massive watery
diarrhea
Retro-translocation of CTX A1-chain relies on hi-jacking the hosts protein quality control system, termed
ER-associated degradation, the normal function of which is to direct terminally misfolded proteins to the
cytosol for degradation by the proteasome.
a) reduced form of
protein disulfide
isomerase (PDI)
unfolds and
dissociates A1 chain
b) A1 is released
from PDI-A1
complex by
oxidation of PDI by
the membrane-
associated ER-
oxidase
c) the unfolded A1-
chain enters
cytoplasm via the
protein conducting
pore Sec61
d) A1-chain avoids
degradation by the
proteasome: rapid
folding and few
lysine residues,
which are the
targets for
ubiquitination
(targets proteins for proteasome degradation)
CTXø integrates into chromosome I, the larger of the 2 V. cholerae
chromosomes AND
Integration is via recombination of CTXø attP at the host sequence
attB +
Recombination utilizes V. cholerae proteins XerC and XerD
CTXø carries
ctxAB
clinical symptoms of vc
-severe disease without fever or abdominal pain
-watery stool –> shock in 12-24hrs
-purge 100% body weight in 4-7days (up to 1 L/hr!)
-described as rice water stool: “rice” actually mucous discharge from GOBLET CELLS and eroded GI mucosa
-altered consciousness/hypoglycemia/electrolyte imbalances
Dx by history
stool exam by dark field/phase contrast for motile organisms
Cx is often difficult
Rx
treamtnet reduces mortlaity from 50-70% to <0.5%
Rx=
-Rehydration: 5g NaCl, 50g pre-cooked rice/liter oral rehydration
fluid
-7 liter i.v. or 11 liters p.o. is average required rehydration
tetra/doxycycline, trimethoprim sulfamethoxazole can reduce fluid
loss and duration of diarrhea
Vibrio parahemolyticus =
-Halophilic organism, prevalent in salt water during summer and
early fall;
-Hx: watery/sometimes mucoid/less often bloody diarrhea low grade
fever, headache, chills about 24 hrs after ingestion, abdominal pain
-Rx: self-limited illness, antibiotics don’t help
-Dx: history
major cause of diarrhea in Japan & associated with raw/undercooked seafood and food contaminated with seawater
Vibrio parahemolyticus
Sx of Vibrio parahemolyticus
watery/sometimes mucoid/less often bloody diarrhea
low grade fever, headache, chills about 24 hrs after ingestion,
abdominal pain
secondary cases very uncommon in Vibrio parahemolyticus bc
requires high doses to cause infx; avoided by GOOD SANITATION
Vibrio parahemolyticus Dx + Rx
-Dx by History
-Rx: supportive care/rehydration
