3.12 Flashcards
Streptococcus
pyogenes
”—“-forming
pus
Some streptococci are typically seen
as
diplo-cocci:
Streptococcus pneumoniae
b-hemolysis (top) on blood-agar plates causes
clearing at and around colonies in
Streptococcus pyogenes
a-hemolysis (bottom) shows greening due to partial lysis of erythrocytes in (2)
S.mitis and
S.pneumoniae.
pneumolysin degrades hemoglobin green Green color sheen has given the name --- to many αhemolytic Streptococci like the caries-causing: S.mutans, S.mitis, S.salivarius, S.sanguis
viridens
Rapid strep throat test (2)
is based on Group A
serological response.
Useful for rapid distinction from viral strep throat
in school children (but culture must be done)
Sequencing of the emm gene for the required virulence factor protein —has
become more important than Lancefield antigens to identify strains.
M
M protein - (3)
cell wall component, >100 serotypes, membraneanchored: is an important virulence factor
anti-M antibodies prevent infection of S.pyogenes but many serotypes.
So protective immunity is
type-specific
• M protein binds —, the main cell type in outer skin layer
keratinocytes
M protein binds —, blocking surface from complement system
components
fibrinogen
M protein binds complement control proteins
• Inhibits formation of —by complement cascade
opsonins
Ø capsule:
antibodies are ineffective against glycocalyx-covered surface antigens
Group A strains have capsules of (1), mimicking
mammalian connective tissues, preventing phagocy
hyaluronic acid
Ø F protein
(cell wall adhesin) provides adherence to the fibronectin of throat epithelial cells
Ø lipoteichoic acid
(species-specific form) also adheres to the fibronectin epithelial cell coat
Ø M protein also shows adhesion for — and strong adhesion to —
fibronectin
keratinocytes (skin)
Adhesion-based uptake of cocci into epithelial cells is likely a basis for the repeated
nature of
strep throat and deep tissue infections.
- M protein anti-complement action through
Factor H
- Capsular C3 peptidase destroys opsonizing — complement opsonization
C3b
Thus: CR1 does not work! Phagocytosis only by
IgG opsonization (FcR)
Ø G protein (cell surface) binds Fc of IgG, preventing
phagocytosis based on FcReceptors
Ø — peptidase in Group A Streptococci
C5a
c3b peptidase cleaves the complement component into — fragments
inactive
inactivate complement chemotaxin c5a; activate surface of — to — and cleave of c3b
plasminogen
plasmin
membrane damagin toxins (cytotoxins) fxn toxin: streptococcus pyrogenes name of disease; name of toxin characteristic of the disease mechanism
disrupts the plasma membrane
pharyngitis and other infections; streptolysin O
accumulation of pus
inserts into membranes, forming pores that allow fluids to enter
streptolysins S, O:
lysis of erythrocytes (direct lysis; basis of β-hemolysis) and
of phagocyte lysosomal membranes (indirect lysis of leukocytes)
secretion of tissue degrading enzymes (4)
DNase, protease,
hyaluronidase (spreading factor),
streptokinase (degrades blood clots)
streptokinase is clinically useful in early vascular attack treatment because it
activates plasminogen
and the resulting plasmin will degrade fibrin clots formed in stroke and heart infarct.
superantigens: fxn toxin: streptococcus pyogenes (certain strains) name of disease; name of toxin characteristic of the disease mechanism
overrides the specificity of the t cell response
streptococcal toxic shock; streptococcal pyrogenic exotoxins (SPE)
fever, vomitting, diarrhea, muscle aches, rash, low bp
systemic toxic effects due to the resulting massive release of cytokines
Cytokines:
IL2, TNF-β, IFN-γ , and through macrophage activation: TNF-α, IL1, IL6 (inflammation, shock)
Cause of scarlet fever, toxic shock, flesh-eating fasciitis
scarlet fever: toxin
Streptococcus pyogenes
scarlet fever
Virulence factor:
a superantigen SPE
Streptococcal Pyrogenic Exotoxins
Other results of pyrogenic SPEs (2)
Pyoderma (impetigo)
pyo = pus
derma = skin
skin infections of face, arms, legs
Erysipelas
erythros = red
pella = skin
bullae = blisters
Flesh-Eating: toxin
Strept.pyogenes
“streptococcal gangrene”
Progression to deep, systemic
infection leads to
multi-organ
failure and death.
—- is caused by streptococcus pyogenes
necrotizing fasciitis
Acute Pharyngitis = Strep throat (2) symptoms
glomerulonephritis (type 3 hypersensitivity) rheumatic fever (type 2 hypersensitivity)
acute rheumatic fever symptoms (2)
myocarditis
arthritis
Rheumatic Heart Disease by —
Streptococci
Acute Rheumatic Fever: • non---- sequela with some strains • <---% of population is susceptible • fever is non-responsive to --- because disease is autoimmune •frequency of reoccurrence?
suppurative
10
penicillin
high
Streptococcus agalactiae Group B (4)
β-hemolytic (<2% non-hemolytic), chain-like growth, aerobic, polysaccharide capsule
Group B,
Normal occurrence in the —
Does not cause disease in healthy people
lower gastrointestinal tract
Group B,
where is it found? (4)
• pneumonia in neonates (neonates: <7 days of birth)
• bacteremia and meningitis (neonates: >7 days of birth)
• various symptoms in elderly suffering from chronic diseases
(often complicated by penicillin allergy)
• urinary infections, bacteremia (pregnant women)
— against group B polysaccharide Ag develop quickly and protect.
Neutralizing antibodies
maternal Abs prevent infection of neonate
Strains different from S.pyogenes or S.agalactiae may cause opportunistic
e. g. in HIV-immune-compromised cases.
streptococcal toxic shock syndrome
Enterococcus faecalis
virulence
Ø high, multiple antibiotic resistances (plasmid and chromosomal)*
Enterococcus faecalis
Epidemiology
elderly
long hospitalization
(high nosocomial risk
antibiotic resistance)
Streptococcus pneumoniae (3)
α-hemolytic, Gram+ diplococci
Streptococcus pneumoniae
causes per year in USA
500,000
Streptococcus pneumoniae
Only — strains
(smooth colonies) are
virulent
encapsulated
pneumococcal pneumonia (2)
epidemiology
prevention/tx
high carrier rates for s pneumoniae
capsular vaccine available
klebsiella pneumonia (4)
cauative agent
epidemiology (2)
prevention/tx
an enterbacterium
often resistant to antibiotics
fatal nosocomial pneumonias
no vaccine available
mycoplasmal pneumonia
prevention/tx
no vaccine available
Streptococcal pneumonia
treatment of choice
penicillin
S.pneumoniae virulence factors (3)
α-hemolysis
capsule
secretory IgA protease
meningitis
S.pneumoniae
Neisseria sp. (5)
• Gram− diplococci
• Lipooligosaccharide (vs. LPS): lack O antigen extensions
• common oral flora and other mucous membranes
• facultative anaerobe
• pathogens: N.gonorrhoeae and N.meningitidis
Host: only humans
Ø — variation and — variation of pilin genes
phase
antigenic
Virulence Factors of N. gonorrhoeae
vaccination?
not possible
Virulence Factors of N. gonorrhoeae
capsule?
no
Pathogenesis of Gonorrhea
Antigenic variation of bacterial surface proteins (4)
ØPilE single chromosomal copy of pilin structural gene
ØStrains contain 10-15 copies of PilE variants lacking promoter and 5-end
of gene called PilS genes
ØPilS genes recombine with PilE creating unlimited antigenic variants of PilE
ØResult is that antigenic structure of pilus protein is constantly changing
Phase Variation:
on/off switch for surface protein expression
In Neisseriae:
Slipped Strand Mispairing resulting from presence of multiple
identical repeated sequences at 5-end of gene. Replication errors due to strand
misalignment creates reading frame errors.
Often, premature stops, but also results in ON/OFF switch.
Multiple Opa (Colony Opacity) protein copies scattered across genome;
Slipped
strand mispairing results in frequent variation in Opa protein expression or
complete absence of Opa
Pathogenesis of Gonorrhea (2)
Ø Phase Variation: on/off switch
Ø E. coli and other Gm- rods simple inversion
of promoter
— mediate bacterial attachment to non-ciliated epithelia
bacteria proliferate and shed into secretions; can also ente
Pili
Virulence Factors of N. gonorrhoeae
Ø secreted IgA protease:
Usefulness of cleaving IgA: Coating of bacteria with IgA Fab fragments (does not activate complement and also blocks binding by other IgG and IgM)
Serum-resistant virulent strains cause disseminated gonococcal infections: (2)
• Strains lack Opa proteins (colony opacity proteins = outer-membrane proteins)
Neutrophils unable to engulf bacteria lacking Opa proteins.
• Sialic acid on LOS (Lipidoligosaccharide of outer membrane) binds complement
regulatory proteins, prevents complement-based phagocytosis.
Ø Shedding of lots of — (LOS of these bacteria)
Binds TLR-4 (especially on dendritic cells, macrophages,
& B cells) secretion of pro-inflammatory — (TNFalpha, IFN-gamma, IL-1,-12, & -18) & nitric oxide shock
endotoxin
cytokines
Gonorrheal Diseases
transmission
§ Sexual transmission - urogenital infections
Gonorrheal Diseases
§ Frequently (almost) —
o — in men, urethral pus secretion
(leukocytes with many gonococci)
o — in women, frequently some urination
sensitivity but no other symptoms
(infection tracing is important to prevent re-infection)
asymptomatic
urethritis
cervicitis
Gonorrheal Diseases Opthalmia Neonatorum (2)
o destructive eye infection, acquired during birth
o Application of erythromycin ointment into both
eyes of newborns is mandatory in many states
and is considered standard neonatal care
Gonorrheal Diseases
Pelvic Inflammatory Disease (PID) in women (3)
Initial infection of cervix, fallopian tubes and vaginal wall glands can lead to PID (15-30%):
o gonococci enter abdominal cavity, cause liver disease
o tissue scarring causes fallopian tube abnormalities which lead to ectopic pregnancies
and sterility
Gonorrheal Diseases
Urethral and testicular tubule scarring, resulting from epididymitis, leads to (2)
sterility
and increased urethral infections by other microbes
Disseminated Gonococcal Infection (without apparent genital infection) causes (3)
skin
lesions, suppurative arthritis of a major joint, heart valve destruction.
Little or no — (pilin variability!) is observed
after recovery from an infection with N.gonorrhoeae.
protective immunity
factors affecting intravascular survival (2)
capsule: protects against complement mediated bacteriolysis and phagocytosis
acquisition of iron from transferrin
crossing of the blood brain barrier
multiplication in subarachnoid space
Neisseria meningitidis
Symptoms
start like a mild cold, progress to throbbing headache, fever, stiffness in neck and back, nausea and vomiting, deafness and coma.
Shock and death (100% if untreated) may occur within 24 hours, but frequently
is slower so that effective treatment can be given (<10% death in treated
cases).
Neisseria meningitidis
Obstruction of release of increased fluid pressure (due to PMN attempts at eradication: pus and clotting) impairs
brain, causes paralysis of motor nerves
and coma. Loss of blood supply to brain is one of the frequent symptoms just
prior to death
Neisseria meningitidis
LOS/endotoxin release from blood-circulating meningococci (which have a high tendency to auto-lyse and thus spread LOS widely) causes —.
shock
Neisseria meningitidis
Contrary to other meningitis-causing infections, small local skin hemorrhages are observed: Localized loss of vascular integrity: effect of
inflammatory cytokines release induced by endotoxin activation of macrophages.
Neisseria meningitidis
Purpura fulminans:
blood spots, bruising, and discoloration
of skin from coagulation in small blood vessels
Neisseria meningitidis
Can progress to disseminated intravascular coagulation:
blood clots throughout the circulatory system resulting in
blockages and excessive bleeding elsewhere (clotting
factors depleted)
Virulence Factors of N.meningitidis (4)
Ø Large capsule
Ø IgA protease
Ø Pili
Ø Shedding of lots of Endotoxin shock
Ø Large capsule leads to
disseminated intravascular coagulation (DIC)
Some virulent strains have capsules with sialic acid on LOS (like
N.gonorrhea): reduces phagocytosis further
Effective vaccination against capsular polysaccharides (2)
MenACWY Vaccine – CDC recommended since 2005
Protection from 4 major disease-causing strains:
A, C, W135 and Y (serotyping: 12 antigenic groups)
MenB vaccine – approved in 2014 & also recommended
B capsule poly-sialic acid; Andy Marso’s case involved
serogroup B bacteria.
European MenB vaccine was used in outbreaks at
Princeton and UC Santa Barbara in 2013-2014
q Mandatory vaccination for students living in dorms
in many states, military recruits, and jail inmates
N.meningitidis
N.species: N.gonorrhoeae “gonococci”
Virulence factors
Clinical features
Epidemiology
pili, Ag-variation
adhesins, OPA
IgA protease
endotoxin/LOS
gonorrhea (Ch.69)
pelvic inflammatory
disease
arthritis (Ch.65, 70)
sexual transmission
asymptomatic carrier
N.species: N.meningitidis "meningococci" Virulence factors Clinical features Prevention Epidemiology
polysaccharide capsule endotoxin/LOS Pili IgA protease
meningitis (Ch.61)
meningococcemia
(bacteremia)
Prevention:
MenACWY &
MenB vaccines
asymptomatic carrier
aerosol transmission
children/young adults
Gram− bacteria of the human colon/oral cavity
Bacteroides
Bacteroidales (3)
Strict anaerobes
Commensals
Opportunistic pathogens
Bacteroides fragilis (2)
- most frequently isolated from clinical specimens of abscesses caused by intestinal bacteria
- most oxygen-resistant Bacteroides
Bacteroidales
Virulence Factors: (3)
Ø Superoxide dismutase - detoxifies oxygen radicals
Ø Catalase - breaks down hydrogen peroxide
Ø Polysaccharide capsule
Ø Superoxide dismutase - detoxifies oxygen radicals
Ø Catalase - breaks down hydrogen peroxide
allows for
survival in well oxygenated peritoneal cavity
Also helps bacteria resisting killing by phagocytosis
Bacteroidales
Disease
caused when
examples (2)
bacteria are introduced into deep tissues
- peritonitis - rupture of infected appendix/diverticulum
- pulmonary abscess - aspiration of oropharyngeal bacteria
Bacteroides fragilis is one component in these diseases
— —
— - start with acute inflammation
progress to formation of localized abscesses
— as disease progresses
100’s of different species in inoculum
few species in abscess
due to response of the host and features of individual bacterial
species
polymicrobial diseases
biphasic
bacterial composition changes
Bacteroidales
Course of disease
perforation of intestine/spillage of intestinal fluid
neutrophils mobilized
surviving bacteria resistant to phagocytosis
B. fragilis has a capsule
oxygen-sensitive bacteria are killed
peritoneal cavity well-oxygenated
facultative anaerobes grow first (E. coli)
some strict anaerobes survive
site becomes anaerobic
surviving strict anaerobes become predominant
Bacteroidales
treat with
Surgery and antibiotic combinations (target aerobes and anaerobes)
