3.16 Flashcards
Gram− bacilli
Some are common members of (2)
human and animal flora
Some are members of commensal groups that have become
pathogenic due to acquired virulence factors like toxins from
(3)
plasmids, bacteriophages or
“pathogenicity islands
”
Most can be motile with
peritrichous flagella (
H
-antigen
)
Some are non-motile (3)
Shigella, Klebsiella, Yersinia
Most have surface pili:
fimbriae for adherence and sex pili for
plasmid conjugation
Some species have capsules (2 antigen) (3 species)
(K or Vi antigen) (most Klebsiella
species, some Enterobacter and E.coli species)
All: (3)
outer -membrane LPS (heat -stable endotoxin) with enterobacterial common antigen and serotype -specific O - antigen
When bacteria have a toxin
like cholera toxin:
get watery diarrhea
When also have a toxin like
Shiga toxin:
get blood in diarrhea
When also have inflammation
and neutrophils:
get pus in diarrhea =
dysentery
Outer- and inner-core sugars are the
— common antigen
enterobacterial
LPS: Also known as the
“heat-stable
enterotoxin”
Type III secretion system is present in many bacteria like (4):
Yersinia, Salmonella, Shigella, enteropathogenic EPEC (E.coli); also present in other species like Pseudomonas and Chlamydia):
Type III secretion system
20-protein system that looks like a short, hollow flagellum (“needle”) to inject a variety of speciesspecific toxins into host cells
Escherichia coli
Transmission: (3)
• person-to-person
• contaminated food
• human and animal feces
(no hand washing; insect vectors)
E.coli Virulence Factors
Ø heat-labile enterotoxin “LT” (cholera-like AB-exotoxin): (4)
ADP-ribosylation of G protein ► cAMP ►
loss of water + electrolytes ► watery diarrhea (e.g. foodborne enterotoxigenic ETEC E.coli)
Traveller’s diarrhea
In Shigella dysenteriae this set of symptoms “diarrhea with blood” is combined with
intestinal cell invasion, apoptosis and neutrophilia (► “pus”) to define “dysentery”.
Name: EPEC, EnteroPathogenic Virulence Factors: Clinical: Epidemiology: Treatment:
bundle-forming pili
adhesins with effacing
[see 16-3]
watery diarrhea
vomiting
infants (developing
world) hospital
nurseries, bottle-fed
infants
replenish fluids
unknown
Name: EHEC
EnteroHemorrhagic
(typically O157:H7)
Virulence Factors:
CLINICAL: (3)
Epidemiology:
TX: (2)
shiga toxin
adhesins with effacing
bloody diarrhea
hemorrhagic colitis
hemolytic uremic
syndrome
Foodborne &
waterborne
(developing world)
replenish fluids
(antibiotics are
contraindicated)
Name: ETEC
EnteroToxigenic
Virulence Factors:
Clinical:
Epidemiology:
Treatment:
pili heat-labile enterotoxin (cholera-like toxin) heat-stable enterotoxin (LPS) [see Fig.16-2]
watery diarrhea
children (developing
world)
foodborne (picnic,
travel)
replenish fluids
prevention: PeptoBismol (bismuth)
ciprofloxacin (but
resistance!)
Name: EAggEC
EnteroAggressive
Virulence Factors:
Clinical:
Epidemiology:
Treatment:
pili
cytotoxins
diarrhea + mucus
children + HIV
replenish fluids
fluoroquinolones (if
AIDS)
Name: EIEC
EnteroInvasive
Virulence Factors:
Clinical:
Epidemiology:
Treatment:
invasion of colonic
epithelials (like
Shigella)
bloody diarrhea
hemorrhagic colitis
children (developing
world)
replenish fluids
antibiotics (gentamicin,
polymixin) to shorten
Name: UroPathogenic Virulence Factors: Clinical: Epidemiology: Treatment:
adhesins (bladder
epithelia)
hemolysin
pathogenicity islands
cystitis (bladder
infection)
pyelonephritis
nosocomial: catheter
women: intercourse,
diaphragm
men: enlarged prostate
prevent: drink enough
trimetaprimsulfamethoxazole
fluoroquinolones
Name: Meningitis associated Virulence Factors: Clinical: Epidemiology: Treatment:
K1 capsule
S fimbriae
cellular invasion
acute meningitis
neonates (birthassociated infection)
broad-spectrum
cephalosporins
E.coli –%;
Klebsiella, Proteus –%;
Staphylococcus saprophyticus –%
70-90
5-10
5-10
Shigella dysenteriae: induction of apoptosis (5)
1) Shigellas are taken up by M cells and transported beneath the epithelium. Macrophages take up shigellas, die and release the bacteria. (2) The bacteria enter the inferior and lateral aspects of the epithelial cells by inducing endocytosis. The endosomes are quickly lysed, leaving the shigellas free in the cytoplasm. (3) Actin filaments quickly form a tail, pushing the shigellas into the next cell (4) Shigellas multiply in the cytoplasn and the infection extends to the next cell. 5) Infected cells die and slough off. Intense response of acute inflammatory cells (neutrophils), bleeding and abscess formation.
Epidemiology:
Transmission via fecal-oral route; sometimes by
fecally contaminated food or water, humans
generally the only source
Virulence Factors
Dysentery:
Shiga toxin: bloody watery diarrheal
Cell invasion -neutrophils * pus
S.enterica (4)
- enteric fever
- human reservoir
- typhoid
- high mortality
Many Salmonella species: (3)
- gastroenteritis
- poultry reservoir
- foodborne illness
Salmonella Virulence Factors (2)
in S.typhi serovars: (2)
Ø Type III secretion induces enteric epithelial uptake via M cells
Ø intracellular endosome growth in macrophages: secretes protein that
prevents phagosome-lysosome fusion
in S.typhi serovars:
Ø through macrophages: invasive into different tissues and organs
Ø destruction of Peyer’s Patches ► intestinal rupture
Salmonella invasion of intestinal epithelia (4)
- M cell uptake through ruffles: transport through epithelial layer.
- Electrolyte release to lumen (diarrhea/gastroenteritis).
- Release of inflammatory exudate.
- Transport to lymph nodes / transient bacteremia
Gram- rods, aerobic / facultatively anaerobic
species: Salmonella
enterica
(*serovar typhi)
Virulence factors:
Clinical features:
Treatment:
Epidemiology:
type III secretion epithelial cell invasion intracellular growth (in macrophages) R-plasmids
diarrhea
enteric fever*
(serovar typhi)
(antibiotic treatment may prolong carrier state) *fluoroquinolones attenuated oral vaccine gal bladder resection
contaminated food
bacteremia if
immunecompromised
Gram- rods, aerobic / facultatively anaerobic
species: Shigella
dysenteriae
Virulence factors:
Clinical features:
Treatment:
Epidemiology:
type III secretion intracellular spread induces apoptosis in macrophages R-plasmids
bacillary dysentery
ampicillin
trimetaprimsulfamethoxazole
fluoroquinolones
foodborne
waterborne
person-to-person
Gram- rods, aerobic / facultatively anaerobic
species: Klebsiella
pneumoniae
Virulence factors:
Clinical features:
Treatment:
Epidemiology:
capsule
R-plasmids
pneumonia
urinary tract
infections
cephalosporins
fluoroquinolones
nosocomial
infections
alcoholism
Gram− vibrio (curved rods) (salt tolerant) found in (2)
estuaries and marine environments (e.g. in crabs)
Vibrio cholerae:
Virulence Factors: (4)
Ø toxin co-regulated pilus (tcp): adhesion to small intestinal epithelia
Ø cholera toxin (heat-labile exotoxin “LT”): protein A causes cAMP rise + watery diarrhea
Ø an additional toxin “ST” can raise cGMP levels with a similar effect
Ø Neuraminidase-increase cholera toxin binding
CTXφ (a bacteriophage) and Vibrio cholerae
TCP production is induced within the intestine, while production in other environments appears to be minimal
(toxin is phage CTXφ-encoded and regulated by pilin-regulating chromosomal gene)
TCP =
Toxin
coregulated
pilus
(2) encode the
proteins that comprise cholera toxin
ctxA and ctxB
Cholera
formalinized whole-cell vaccine:
several doses; partial protection for 2-3 yrs
Common epidemic strain:
serovar O1
New strain:
serovar O139 with capsule as new virulence factor
India 1992) (O1 vaccine does not protect
Gram- vibrio (rods), aerobic / facultatively anaerobic Virulence factors (4) Clinical features (2) Treatment (1) Epidemiology (2)
cholera toxin
toxin-coregulated pili
toxins
neuraminidase
severe watery diarrhea
Disease is self-limiting as
intestinal cells with surface
bacteria are shed.
Rehydration + electrolytes
to shorten course:
doxycycline, trimethoprimsulfamethoxazole or
furazolidone
fecal transmission in
developing countries
under-cooked coastal
crabs
Campylobacter jejune
shape
Gram− vibrio (short S- or
comma-shaped rods)
Campylobacter jejune
Virulence Factors: (3)
Ø Growth in intestinal tract:
§ invade intestinal epithelial cells or
grow below epithelial layer.
§ inflammatory response
Campylobacter jejune
Zoonosis:
animal reservoir (intestinal)
Campylobacter jejune
Transmission:
contaminated food (poultry, milk) (e.g. in >89% of raw chicken)
Campylobacter jejune
Disease: (3)
Disease: gastroenteritis, diarrhea, dysentery
Campylobacter jejune
Disease resolves without treatment in —
Creates —
<1 week
protective immunity
Gram- vibrio (rods), aerobic / facultatively anaerobic
C.jenune
adhesion; invasion
of mucosal
epithelia
gastroenteritis
self-limited
In severe cases: erythromycin,
tetracycline or fluoroquinolones
zoonotic infection
(food, milk, water)
Helicobacter pylori classification
Gram− vibrio
Helicobacter pylori
Virulence Factors: (5)
Ø urease (urea ® ammonia pH increase, neutralization of stomach acid)
Ø VacA protein acts on gastric mucosal epithelia and promotes flow of urea into stomach
Ø CagA protein: injected into host epithelia cells change (prelude to cancer)
Ø mucinase
Ø flagella
Gastric ulcer
Organisms survive the acidity of stomach juices
by producing a powerful urease. Upon reaching the
layer of mucus, they penetrate to the epithelial
surface, where bacterial products incite an
inflammatory response. Thinning of the mucus
layer occurs, and 10 to 20% of infected individuals
develop ulcerations. Only a small percentage
develop cancer, but more than 90% of individuals
with stomach cancers are infected with H. pylori
No proven preventive. Most infections are cured
using two antibiotics together, plus a medication to
suppress stomach acid (see next slide)
Symptoms of stomach and upper duodenum infection:
v in most people:
no symptoms (symptom-free carrier).
Pseudomonas aeruginosa
characteristics (5)
Gram− short rods polar flagella (one or more; high mobility) obligate aerobe simple nutrient requirements (acetate) broad temperature range: 20 to 43 ºC
alginate
mechanism of action (3)
contribution to virulence (1)
adherence, protection from dehydration, and immune evasion
biofilm formation
lipopolysaccharide
mechanism of action
lipid A is endotoxic, core interacts CFTR (Cystic Fibrosis Transmembrane conductance Regulator); O antigen protects from complement mediated killing
opportunistic pathogen (in case of disease, cancer, weakened immunity): (3)
- common in environment (water, soil) +
Hot tubs are perfect culture conditions (due to heat tolerance) - resistance to many chemical desinfectants (like iodine) +
- R-plasmid based resistance to many antibiotics
major problem in hospitals (nosocomial infections) (5)
ü lungs: artificial ventilators, cystic fibrosis (mucoid strains) ü skin: burn victims, folliculitis ü bladder infections ü ear infections (swimmers ear: otitis externa) ü eye infections (from contact lenses)
(2) characterize P.aeriginosa
Soluble blue-green dye pyocyanin and
pyoverdin
Pseudomonas aeruginosa Gram- rod, generally aerobic Clinical features (1) Treatment Epidemiology (1)
Pulmonary (CF patients) 1º skin infection urinary tract infection eye & ear infection bacteremia
combination therapy: aminoglycoside + cephalosporins, piperacillin-tazobactam or carbapenem
nosocomial infection
Bordetella pertussis
characterization
Gram− coccobacilli
strict aerobe
non-motile, capsule
B.pertussis show dense surface growth in the
lower
respiratory tract (bronchi, bronchioli) without cell
invasion and with strong mucus secretion.
Virulence Factors of Bordetella pertussis (5)
Whooping cough (pertussis)
adhesion to ciliated respiratory tract cells
but NOT invasive
toxins:
Ø pertussis toxin ptx
Ø secreted invasive adenylate cyclase / hemolysin
Ø tracheal cytotoxin (Nitric Oxide NO release)
Ø tracheal cytotoxin (causes Nitric Oxide NO release)
Ø pertussis toxin ptx
(ADP-ribosylation of G-protein: cAMP increase
mucus and other secretions)
secreted invasive adenylate cyclase / hemolysin
(cAMP increase)
Ø tracheal cytotoxin (Nitric Oxide NO release) (2)
kills ciliated cells
toxin is a component of peptidoglycan
disaccharride-tetrapeptide
Ø tracheal cytotoxin (causes Nitric Oxide NO release) (2)
kills ciliated cells
toxin is a component of peptidoglycan disaccharride-tetrapeptide
Most gram negative bacteria keep — within the cell wall by using a transporter protein to recycle it.
is B. pertussis capable?
TCT
B. pertussis not capable of recycling TCT and it escapes to the surrounding environment.
Bordetella pertussis Gram- small coccobacilli, strict aerobic Virulence factors Clinical features Treatment Epidemiology
pertussis toxin
adenylate cyclase toxin
tracheal toxin
adhesins
pertussis (whooping
cough)
DTaP vaccine (Diphtheria, Tetanus, acellular Pertussis) supportive treatment erythromycin (partially effective if given early; prophylaxis)
aerosol transmission
childrens disease
(mild symptoms in adults
who are the reservoir)
Corynebacterium diphtheriae characterization (3)
Gram+ pleiomorphic (club-shaped) rods
opportunistic pathogen
oral pathogen with systemic effects
Corynebacterium diphtheriae
1 Virulence Factor: diphtheria toxin
diptheria; diptheria toxin (phage β coded)
(expressed only as prophage)
(toxin gene is induced if iron is LOW)
pseuodomembrane in the throat; heart, kidnet damage Inhibits protein synthesis by inactivating an elongation
factor of eukaryotic cells. Kills local cells (in the throat)
but can also be carried in the bloodstream to
various organs.
NAD + EF2 = ADP + ribose-EF2 + nicotinamide
diphtheria: Corynebacterium diphtheriae Virulence Factors (2)
throat adhesion
diphtheria toxin
diphtheria toxin
(ADP-ribosylation of EF-2 causing translation stop) cell death pseudomembrane Pseudomembrane = C.diphtheriae cells + damaged host cells + blood à Block air passage
Disease risks from toxin:
local: (2)
systemic: (2)
• paralysis
impaired swallowing
peripheral neuritis
• Suffocation (due to blockage)
- cardiac arrythmia
- kidney failure
Corynebacterium diphteriae Gram+ rods, aerobic / facultatively anaerobic Virulence factors Clinical features TX (1) EPIDEMIOLOGY (1)
diphtheria toxin
diphtheria • respiratory • cutaneous (skin ulcers in vaccinated carriers)
neutralizing antitoxin
penicillin or erythomycin
prevent by toxoid vaccination
Spread by saliva droplets
diseases DPT (3)
diptheria
pertussis (whopping cough)
tetanus
