※
Colonies:circular, 2-3 mm in diameter with a
smooth, shiny opaque surface;
※
Pigments:golden、grayish white or lemon
※
Hemolysis on sheep blood agar plate
Important properties
※
Mannitol fermentation
※
Produce catalase
H
2
O
2
→O
2
+ H
2
O (hydrogen
peroxide)
※
Coagulase : S aureus, can clot citrated plasma
(-) (+)
Antigenic StructureAntigenic Structure
★
★
Staphylococcus protein AStaphylococcus protein A,,SPASPA
Binds to the Fc portion of IgG at the complementBinds to the Fc portion of IgG at the complement
binding site binding site
SignificanceSignificance
※
※
Preventing the activation of complementPreventing the activation of complement
※
※
anti-phagocytosis anti-phagocytosis
※
※
coagglutinationcoagglutination
PHAGOCYTEPHAGOCYTE
Fc receptorFc receptor
Protein AProtein A
immunoglobulinimmunoglobulin
Bacterium, etc.
immunoglobulinimmunoglobulin
Bacterium, etc.
Staphylococcus protein A Staphylococcus protein A ,,SPASPA
Binds to the Fc portion of IgG at the complementBinds to the Fc portion of IgG at the complement
binding site binding site
SignificanceSignificance
※
※
Preventing the activation of complementPreventing the activation of complement
※
※
anti-phagocytosis anti-phagocytosis
※
※
coagglutinationcoagglutination
Antigen+antibody+SPA→compound with High molecular weight
Resistance
Thermotolerance:60 1h or 80 30min
℃ ℃
Salt tolerance:can grow in 10-15% sodium chloride solution.
resistant to common disinfectants
Antibiotics resistance:multidrug resistant
MRSA (methicillin resistant staphylococcus aureus)
▲ Catalase
▲ Coagulase and clumping factor
▲ Hyaluronidase and Lipase ipase
▲ Hemolysin or sphingomyelinase Csphingomyelinase C
▲ Leukocidin
▲ Exfoliative Toxin (superantigen)
▲ Toxic Shock Syndrome Toxin
(superantigen)
▲ Enterotoxins (superantigen)
PathogenesisPathogenesis
PathogenesisPathogenesis
H
2
O
2
→O
2
+ H
2
O
▲ Destruction of the bactericidal activity of hydrogen peroxide
▲ Differentiate the staphylococci from the streptococci
※
catalase
▲ Coagulase: an enzyme-like protein that clots citrated plasma
Coagulase
prothrombin
+
Enzymatically active(thrombin-like)→fibrin
polymerization
Free coagulase
※
Coagulase and clumping factorCoagulase=
↓
☆ Coagulase can deposit fibrin on the surface of the
agent, altering their ingestion by phagocytic cells and
their destruction within such cells, so coagulase
production is considered synonymous with invasive
pathogenic potential.
▲ Clumping factor: a surface compound of S.aureus
and adherence of the agents to fibrinogen and fibrin
S.aureus(clumping factor)
+
plasma
Clumps forms
BoundBound coagulase
※
Coagulase and clumping factor Coagulase=
※
Hemolysin
Hemolysin is a exotoxin that cause lysis of red blood cells, white blood
cells, platelet and macrophages in vitro and in vivo.
Alpha-hemolysin,
a transmembrane heptamer
αhemolysin: a broad spectrum of eukaryotic cells
βhemolysin: a broad spectrum of eukaryotic cells
γhemolysin: white blood cells
δhemolysin: play a role in S.aureus diarrheal diseases.
Can increase cation permeability
※
Leukocidin
Leukocidin: a pore forming toxin, so it can form
pores in white blood cell membrane especially the
neutrophil and increase cation permeability.
This toxin may be an inportant virulence factor
in community associated methicillin resistant S.
aureus infection.
※
Exfoliative toxinsEpidermolytic toxins=
Dsg-1:desmoglein 1; Dsg-3:desmoglein 3
Responsible for staphylococcal scalded skin syndrome (SSSS), a
disease predominantly affecting infants and characterized by the loss of
superficial skin layers, dehydration, and secondary infections
Superantigen
※
Toxin shock syndrome toxin-1
Toxic shock syndrome toxin (TSST) is a superantigen
with a size of 22 KDa produced by 5 to 25% of Staphylococcus
aureus isolates. It causes toxic shock syndrome (TSS) by
stimulating the release of large amounts of interleukin-1,
interleukin-2 and tumor necrosis factor. In general, the toxin
is not produced by bacteria growing in the blood; rather, it is
produced at the local site of an infection, and then enters the
blood stream.
Superantigen
TSST-1 binds to MHC- molecules, yielding T cell
Ⅱ
stimulation, which promotes the protean manifestations of the
toxic shock syndrome.
※
Enterotoxins
Superantigen
Staphylococcal enterotoxin is an enterotoxin
produced by Staphylococcus aureus. It is a common
cause of food poisoning, with severe diarrhea, nausea
and intestinal cramping often starting within a few
hours of ingestion. Being quite stable, the toxin may
remain active even after the contaminating bacteria are
killed. It can withstand boiling at 100 for a about 30
℃
minutes. Gastroenteritis occurs because the toxin is a
superantigen, causing the immune system to release a
large amount of cytokines that lead to significant
inflammation.
※
Enterotoxins
Superantigen
The emetic effect of enterotoxin is
probably the result of central nervous system
stimulation (vomiting center) after the toxin
acts on neural receptors in the gut.
Formation conditions of staphylococcal enterotoxin
Storage Temperature: below 37 , the higher of the
℃
temperature, the shorter of the time of toxin
production;
Storage location: easy form enterotoxin in
environment of poorly ventilated, low partial
pressure of oxygen.
Types of food: rich in carbohydrate and protein
Physicochemical properties : Low molecular weight
proteins, heat-resistant, protease-resistant.
Formation conditions of staphylococcal
enterotoxin
Mechanism of action:
▲ Acting on the gastrointestinal mucosa, result in
inflammatory changes such as congestion, edema,
erosion and metabolic disturbance of electrolyte
and eventually diarrhea.
▲ stimulate the visceral ['v sərəl] branch of the vagus
ɪ
nerve, and result in reflex vomiting
Pathogenesis of staphylococcal infectionsPathogenesis of staphylococcal infections
Skin (local) infectionSkin (local) infection
※
※
Furuncle:Furuncle:Protein A, Leukocidin, HemolysinProtein A, Leukocidin, Hemolysin
Food poisoningFood poisoning
Toxic shock syndromeToxic shock syndrome
scalded skin syndrome Babiesscalded skin syndrome Babies
ExfoliatinExfoliatin
feverfever
scarlatiniformscarlatiniform rash rash
desquamationdesquamation
vomitingvomiting
diarrheadiarrhea
myalgiasmyalgias
not a human infectionnot a human infection
food contaminated from humans food contaminated from humans
- growth - growth
- enterotoxin- enterotoxin
onset and recovery both occur within few hoursonset and recovery both occur within few hours
VomitingVomiting/ / nauseanausea/ / diarrheadiarrhea/ / abdominal abdominal //painpain
Toxic diseases
※
※
Cause vomiting and watery, nonbloody diarrheaCause vomiting and watery, nonbloody diarrhea
Food poisoningFood poisoning
Toxic shock syndromeToxic shock syndrome
scalded skin syndrome Babiesscalded skin syndrome Babies
ExfoliatinExfoliatin
feverfever
scarlatiniformscarlatiniform rash rash
desquamationdesquamation
vomitingvomiting
diarrheadiarrhea
myalgiasmyalgias
not a human infectionnot a human infection
food contaminated from humans food contaminated from humans
- growth - growth
- enterotoxin- enterotoxin
onset and recovery both occur within few hoursonset and recovery both occur within few hours
VomitingVomiting/ / nauseanausea/ / diarrheadiarrhea/ / abdominal abdominal //painpain
No feverNo fever
◆
Tampon['tæmp n]
ɑː
Tampon['tæmp n]
ɑː
止血棉塞止血棉塞 ––using using
menstruating womenmenstruating women
◆
◆
Individuals with wound infectionIndividuals with wound infection
◆
◆
Patients with nasal packing used to stop bleeding Patients with nasal packing used to stop bleeding
from the nosefrom the nose
※
※
SuperantigenSuperantigen
Food poisoningFood poisoning
Toxic shock syndromeToxic shock syndrome
scalded skin syndrome scalded skin syndrome BabiesBabies
ExfoliatinExfoliatin
feverfever
scarlatiniformscarlatiniform rash rash
desquamationdesquamation
vomitingvomiting
diarrheadiarrhea
myalgiasmyalgias
not a human infectionnot a human infection
food contaminated from humans food contaminated from humans
- growth - growth
- enterotoxin- enterotoxin
onset and recovery both occur within few hoursonset and recovery both occur within few hours
VomitingVomiting/ / nauseanausea/ / diarrheadiarrhea/ / abdominal abdominal //painpain
ExfoliatinExfoliatin
※
※
Cause scalded skin syndrome in young childrenCause scalded skin syndrome in young children
※
※
Acts as protease that cleaves Acts as protease that cleaves
desmosomedesmosome,,leading leading
to the separation of the epidermis at the granular to the separation of the epidermis at the granular
cell layercell layer
§2 Streptococcus§2 Streptococcus
MorphologyMorphology
Gram-positive, spherical or ovoid, arrange in Gram-positive, spherical or ovoid, arrange in
chainschains, no spore and flagella; in very young cultures,
the capsules are noticeable.
※
※
Facultative anaerobeFacultative anaerobe
※
※
Much higher nutritional requirement, grow Much higher nutritional requirement, grow
well on enriched media.well on enriched media.
※
※
colonies: 1-2 mm in diameter colonies: 1-2 mm in diameter with a smooth,
shiny opaque surface, different hemolytic zone , different hemolytic zone
around the colonies.around the colonies.
Culture and typical biochemical reaction
CatalaseCatalase negative negative
(staphylococci are catalase positive)(staphylococci are catalase positive)
a-hemolytic streptococcus
Incomplete hemolysis, green zone around colonies
* Opportunistic pathogens
ClasssificationClasssification
(1) According to the Hemolytic activity:(1) According to the Hemolytic activity:
b-hemolytic/pyogenic streptococcus
Complete hemolysis, clear zone around colonies
*major human pathogens
g-streptococcus
No hemolyzation, no pathogenicity.
(2)According to the antigenic structure
Group-specific cell wall antigen: on the basis of this antigen,
streptococci can be classified in to A-H and K-U groups.
Chemical property: carbohydrate, the serologic specificity of
this antigen is determined by an amino sugar.
M protein:
▲ The foundation of subtype within groups.
▲ Major virulence factor of group A S.pyogenes.
Group A:more than 100 serotypes
Group B: 4 serotypes
Group C:13 serotypes
Pathogenesis
Virulence factors
exotoxin
Invasive enzyme
Hyaluronidase
Streptokinase
DNAases
Streptolysin (O, S)
Pyrogenic exotoxin
LTA
M protein
Attachment
◆
Common antigen -- heart muscle cell, glomerular basement membrane
cells, etc.
◆
M Ag-Ab complex: type
Ⅲ
hypersensitivity
Such as: poststreptococcal acute glomerulonephritis, rheumatic fever,
rheumatic heart disease.
There is common antigenicity between M protein and Myocardial
cells, glomerular [ 'l mrj lə] basement membrane cells, so the
ɡ ɒ ʊ
antibody just against M protein can also combine with these cells,
activate complements and result type
Ⅱ
hypersensitivity
▲ Hyaluronidase :
Destroy the polysaccharide (hyaluronic acid) that holds animal cells
together, making it easier for the pathogen to spread through the tissues of
the host organism.
(2) Invasive enzyme
▲ Streptokinase (SK)= fibrinolysin [ fa brə'n l s n]
ˌ ɪ ɒ ɪ ɪ
▲ Streptodornase (SD):
an enzyme produced by hemolytic streptococci that catalyzes the
depolymerization of deoxyribonucleic [di ksi ra bə nu 'kli k] acid
ːˌɒ ː ɪ ʊ ː ːɪ
(DNA).
a protein secreted by several species of streptococci which can bind
and activate human plasminogen [plæz'm nəd ən]
ɪ ʒ
血浆酶原
plasminogen
Streptokinase
plasmin
digest
Fibrin and other proteins
Spreading factorSpreading factor
(3) exotoxin:
(i) Pyrogenic exotoxins (erythrogenic toxin)
▲ Coded by lysogenic phage.
▲ superantigen
▲ Low molecular weight proteins, heat-resistant.
Biological activity
▲ Pyrogenic
▲ increased the permeability of blood-brain barrier
▲ cytotoxicity: have cytotoxic activity to spleen cells and macrophages
cultured in vitro
▲ Increase the sensitivity of Animal to endotoxin
(ii)hemolysins
Streptolysin S – alters membrane permeability; lyses RBCs, leukocytes, and
other cells containing sterols in membrane
Streptolysin O – forms membrane penetrating channels (porin) leading to
membrane defects and cell lysis
Streptococcus can produce two hemolysins:
△
Cytotoxic to RBCs and many tissue cells, particularly cardiotoxic
△
Antigenic - anti-streptolysin O (ASO) antibody used to diagnose recent
infection
property
Streptolysin S has no antigenicity
Pathogenesis of S. pyogenes infections.
[er 's p l s]
ˌ ə ɪ əə
Scarlet fever
Toxin-Mediated diseases
Caused by Hemolytic streptococcus B group A,
Acute respiratory infectious disease. Clinical features: fever, pharyngitis,
genernal diffused fresh red eruption and obvious desquamation
Complication: heart, kidney and joints diseases
Scarlet fever is characterized by:
▲ Sore throat
▲ Fever
▲ Bright red tongue with a "strawberry" appearance
▲ Forchheimer spots (fleeting small, red spots on the soft palate) may occur
▲ spares the face (although some circumoral [ s kəm'o rəl] pallor
ˌ ɜː ʊ
口周苍
白 is characteristic)
▲ Characteristic rash:
△
fine, red and rough-textured
△
blanches upon pressure
△
Pastia lines (where the rash runs together in the armpits and groin)
appear and can persist after the rash is gone.
Strawberry tongue
Pastia lines帕斯蒂亚
(1) acute glomerulonephritis ( group A)
[glə merj lə nef'ra t s]
ʊ ʊ ʊ ɪ ɪ
(2) Rheumatic fever
(3) rheumatic heart disease
poststerptococcal diseases (hypersensitive disease)
Prevention & treatmentPrevention & treatment
※
※
Treat the pharyngitis and tonsillitis in time, Treat the pharyngitis and tonsillitis in time,
avoid the post streptococcal diseases.avoid the post streptococcal diseases.
※
※
Antibiotics and chemical agents: penicillin G for Antibiotics and chemical agents: penicillin G for
the first choicethe first choice
Gram stain of pure culture Urethral exudate
§3 Neisseria§3 Neisseria
※
※
Gram negative cocci, usually Gram negative cocci, usually
arranged in pairs and the flat or arranged in pairs and the flat or
concave sides are adjacent. concave sides are adjacent.
※
※
Some are normal inhabitants in Some are normal inhabitants in
respiratory tract. Others are respiratory tract. Others are
human pathogenshuman pathogens
※
※
Gram negative cocci, kidney-shaped, in pairs have Gram negative cocci, kidney-shaped, in pairs have
capsules and pilicapsules and pili
※
※
Need enriched mediaNeed enriched media::grow best on media grow best on media
containing complex organic substances such as containing complex organic substances such as
heated blood, hemin and in an atmosphere heated blood, hemin and in an atmosphere
containing 5% COcontaining 5% CO
2.2.
Common biological characteristicsCommon biological characteristics
Gonococci and meningococci are the main pathogens in
neisseriae, and they are closely related, with 70% DNA
homology.
The main differences between these two agents
△
Meningococci have polysaccharide capsules, but gonococci do
not.
△
Meningococci rarely have plasmids whereas most gonococci
do.
△
Meningococci cause meningitis, whereas gonococci cause
genital infections.
※
※
Resistance: relatively Resistance: relatively fragilefragile organism, susceptible organism, susceptible
to to temperature changes, drying, uv light,temperature changes, drying, uv light, and and
other environmental conditions.other environmental conditions.
※
They are rapidly killed by drying, sunlight, moist heat and
many disinfectants.
※
produce autolytic enzymes that result in rapid swelling and
lysis in vitro at 25
℃
gonococci and their coloniesgonococci and their colonies
Neisseria gonococciNeisseria gonococci
GonoGonococcal colonies on chocolate agar plate: grayish
white, round, convex, smooth, opaque.
1. Pili
2. Por proteins
3. Opa
4. Rmp
5. Lipooligosaccharide (LOS):
Antigenic structure
N. gonorrhoeae is capable of changing its surface antigens
(particularly pilin) rapidly to avoid host defenses.
N. gonorrhoeae (Gonococcus)
Pathogenicity and immunityPathogenicity and immunity
1. Pathogenicity:
(1) Human is the only natural host.
(2) Virulence factor:
※
Pili — key factor in anchorage of organisms to mucosal epithelium.
Nonpiliated gonococci are avirulent
※
IgA1 protease: can split and inactivate secretory IgA1, a major
mucosal immunoglobulin of human.
Has no long O-antigen side chains
▲ Porin proteins (Por) : form porins and mediate
resistance to neutrophil and serum killing, allow
intracellular survival of the bacteria[ also called
protein I].
▲ Opacity proteins (Opa) : associated with opaque
colonies; an outer membrane protein functioning
in attachment to host cells[ also called protein
Ⅱ
].
▲ Reduction-modifiable proteins (Rmp) : stimulates
antibodies that block serum bactericidal
activity [also called protein
Ⅲ
].
Pathogenesis
Attachment to mucosal cells (requires pili) →Invade into the
cells and multiply (Opa mediates tighter association with and
invasion of host cells; Por inhibits phagolysosome fusion)
→Pass through the cells into the subepithelial space
→Establish infection (LOS stimulates inflammatory
response; Rmp blocks bactericidal activity)
Establishment of infection
Pathogenesis and Pathology
Gonococci attack mucous
membrane of the
genitourinary tract, eye,
rectum, and throat,
producing acute suppuration
that lead to tissue invasion;
this is followed by chronic
inflammation and fibrosis.
△
Gonorrhea occurs only in humans.
△
Gonorrhea is transmitted by sexual contact
△
95% infected men and 50% infected women have
acute symptoms. So, asymptomatic carriage is more
common in women than in men.
△
Rectal and pharyngeal infections are more
commonly asymptomatic than genital infections.
Epidemiology
※
Gonorrhea (sexually transmitted disease STD)
in male: acute urethritis
in female: pelvic inflammatory
Symptoms
1. Male: urethritis with yellow, creamy pus and
painful urination. The process may extend to
the epididymis [epə'd dəm s]
ˌ ɪ ɪ
.
As suppuration subsides in untreated
infection, fibrosis occurs, sometimes leading to
urethral strictures (sterility).
2. Female: infection starts from the endocervix, and
results in vagina discharge, dysuria, and abdominal
pain. Uterine ['ju təra n]
ː ɪ
tubes may be involved,
causing salpingitis , fibrosis, and obliteration of the
tubes (20% may become infertile). When
gonococcal cervicitis is either asymptomatic or
unrecognized, the patient may progress to pelvic
inflammatory disease (PID).
3. Gonococcal ophthalmia neonatorum : bilateral
conjunctivitis often follows vaginal delivery from an
infected mother. The symptoms are eye pain,
redness, and a purulent discharge. The organism
can cause permanent injury to the eye in a very
short time; prompt recognition and treatment are
essential to avoid blindness. prevention:
tetracycline, erythromycin or silver nitrate.
4. Gonococcal bacteremia (1-3% of infected women
and much lower percent of infected men) can lead
to fever, pustular rash over the extremities,
tenosynovitis [teno s nə'va t s]
ˌ ʊˌ ɪ ɪ ɪ
腱鞘炎and
suppurative arthritis.
※
Isolation and identification:
direct smear, isolation and culture,
biochemical tests, antigen detection, etc.
Laboratory diagnosisLaboratory diagnosis
Prevention and treatment
Penicillin, Spectinomycin奇霉素,
Ceftriaxone[seftra' æksn]
ɪ
头孢三嗪 , and so on
※
Treatment
△
neonatorum ophthalmia - silver nitrate
△
Strengthen health education and prohibit dirty sex
△
No vaccine
※
Prevention
Infection rate can be reduced by:
1. avoiding multiple sexual partners;
2. early diagnosis and treatment;
3. finding cases and contacts through education
and screening of population at high risk.
4. combined with doxycycline 强力霉素 or azithromycin
[e z θrə'ma s n]
ɪ ɪ ɪ ɪ
阿奇霉素 for dual infections with
Chlamydia
※
Prevention
meningococci and their coloniesmeningococci and their colonies
Neisseria meningococciNeisseria meningococci
Meningococcal colonies on chocolate agar plate:
Colorless, round, convex, smooth, transparent and just like
Dew drops.
1. Capsular polysaccharide: more than 13 serogroups
have been identified (serogroups A, B, C, X, Y, and
W135 are most commonly isolated).
2. Pili (allow bacterial colonization of nasopharynx).
3. Outer membrane proteins: these are analogues to the
Por and Opa proteins of gonococci.
4. Lipooligosaccharide (LOS): responsible for diffuse
vascular damage in meningococcal infections.
Antigenic structure
1. Pathogenicity:
(1) Meningococci are pathogenic only for humans under natural conditions.
Child: susceptible
(2) virulence factor:
*Pili– attach to nasopharyngeal mucosa
*capsule – antiphagocytosis
*endotoxin – main pathogenic substance ®capillary, small blood vessel
*IgA1 protease: can split and inactivate IgA1, a major mucosal
immunoglobulin of human.
Pathogenicity and immunity
Symptoms: begins suddenly, with intense headache,
vomiting, and stiff neck, and progress to coma
within a few hours.
Mortality: nearly 100% if untreated; <10% in patients treated
promptly with appropriate antibiotics.
Neurologic sequelae: uncommon; hearing deficit, Intellectual
impairment
Pathogenesis
Like gonococci, meningococci are able to invade the
epithelial cells. The capsule of meningococci protects the
bacteria from phagocytic destruction.
2. Pathogenesis:2. Pathogenesis:
Epidemic cerebrospinal meningitis Epidemic cerebrospinal meningitis
Clinical typing: common, outbreak, septicemic typeClinical typing: common, outbreak, septicemic type
(1) Organisms (1) Organisms ®® attach to epithelial cells of nasoparynxnasoparynx with the aid of
pili ( nasopharyngeal infection : asymptomatic , most are carriers, ( nasopharyngeal infection : asymptomatic , most are carriers,
only 2~3% go to next stage )only 2~3% go to next stage )
(2) Blood stream <fever, skin ecchymosis[ ekə'mo s s] >
ˌ ʊ ɪ
(2) Blood stream <fever, skin ecchymosis[ ekə'mo s s] >
ˌ ʊ ɪ
®®cross the brain cross the brain
barrier <severe headache ,vomitting, stiff neck > (meningococcemia. barrier <severe headache ,vomitting, stiff neck > (meningococcemia.
bacteremia or septicemia. blood contain cocci ) bacteremia or septicemia. blood contain cocci )
(3) Meninges [mə'n nd i z] (meningitis. meninges pyogenic inflammation.
ɪ ʒ ː
(3) Meninges [mə'n nd i z] (meningitis. meninges pyogenic inflammation.
ɪ ʒ ː
※
Immunity:Immunity:
Group-specific antibody(subclinical Group-specific antibody(subclinical and
symptomaticsymptomatic infection).infection).
※
※
Prevention and treatmentPrevention and treatment
1. Polysaccharide vaccine (group A, C)1. Polysaccharide vaccine (group A, C)
2. Penicillin; cefotaxime [sefə 'tæksa m]
ʊ ɪ
2. Penicillin; cefotaxime [sefə 'tæksa m]
ʊ ɪ
头孢噻肟头孢噻肟 ; chloramphenicol; chloramphenicol
Exercises:Exercises:
Staphylococcus protein A,SPA Coagulase
Toxin shock syndrome toxin-1 Streptolysin O
Lipooligosaccharide (LOS) Streptokinase (SK)
Streptodornase (SD)
1.The pathogenic substances and pathogenicity of cocci?
2.The main pathogenic substances and pathogenicity of
strptococci?