CoccusZooming in pyogenic coccus:

disease and pathogenesis

Pyogenic coccus

Pyogenic coccus

Major pathogenic speciesStaphylococcus (the staphylococcus)

Staphylococcus aureusStaphylococcus epidermidis Staphylococcus saprophyticus

Streptococcus (the streptococcus)Streptococcus pyogenesStreptococcus pneumoniae (the pneumococcus)

Neisseria (the neisseria)Neisseria meningitidis (the meningococcus)Neisseria gonorrhoeae (the gonococcus)

Staphylococcus aureusDiseases

PathogenesisRoles of bacterial virulent factors

DiagnosisMethods for bacteria classification

Treatment and prevention Issues

Bacteria morphology

Staphylococcus : grape-like irregular clusters

Streptococcus : chains or pairs

Neisseria : kidney-shaped diplococci

Bacteria culture: pigmentationThe bacteria produces liposoluble pigments which make the colonies appear in certain color:

Staphylococcus aureus

golden yellow

Staphylococcus epidermidis

white

Staphylococcus saprophyticus

white or lemon yellow

Bacteria culture: mannitol fermentation

Biochemical reactions: for example, Staphylococcus aureus is capable of using sugar mannitol (甘露醇 ) as a food source and will produce acidic byproducts of fermentation that will lower the pH of the media.

Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae and Streptococcus pyogenes on mannitol salt agar plates (containing 7.5% NaCl, mannitol and phenol red).

I. Suppurative infections(化脓性感染 )II. Toxicoses(毒素性疾病 )

Diseases

I. Suppurative infectionsLocal infections (contained at the local)

Superficial skin lesions such as sore ( 疮 ), furuncle ( 疖 ) and stye (睑腺炎，麦粒肿 )

Systemic infections (spread through the blood stream)

Septicemia (败血症 )

Pyemia (脓血症 ): spread to different organs to cause pneumonia (肺炎 ), mastitis (乳腺炎 ), phlebitis (静脉炎 ), meningitis (脑膜炎 ), urethritis (尿道炎 ) and abscesses (脓肿 )

II. ToxicosesFood poisoning

A gastrointestinal illness. Symptoms include nausea, vomiting, stomach cramps, and diarrhea.

Toxic shock syndrome (TSS,毒性休克综合征 )Characterized by a sudden onset of fever, chills, vomiting, diarrhea, muscle aches and rash. It can rapidly progress to severe and intractable hypotension and multisystem dysfunction. Commonly occurs in women.

Scalded skin syndrome (SSS, 烫伤样皮肤综合症 )

Caused by staphylococcal skin infection. The skin blisters and peels off as though burned. Additional symptoms are fever, chills, and weakness. commonly occurs in infants.

PathogenesisCell wall virulent factors

Staphylococcal protein A (SPA)

Coagulase

ExotoxinsStaphylolysin (cytolytic)

Leukocidin (cytolytic)

enterotoxin (superantigen)

toxic shock syndrome toxin 1 (superantigen)

Exfoliatin (superantigen)

Staphylococcal protein A (SPA) Surface bound (in the cell wall) or free proteins.

Bind to Fc portion of IgG from human, mouse and guinea pig (but not to that from rabbit), and thus inhibit Fc receptor-mediated phagocytosis by macrophages.

IgG

Fc receptor

SPA

Inhibition of phagocytosis

Agglutination testIn this test, anti-Staphylococcus aureus IgG can bind SPA using Fc fragment and the bacteria through Fab to from complexes that can been seen with eyes.

Coagulase Bound (in the cell wall): catalyzes fibrinogen (纤维蛋白原 ) into fibrin (纤维蛋白 ). Cause coating of the bacteria with fibrin and thus inhibit phagocytosis and killing mediated by serum components. Free: secreted and turns into staphylothrombin after activation by cofactors in the plasma, which catalyzes fibrinogen into fibrin. Cause coagulation of the plasma and helps to restrain infections at the local.

A test of coagulation of human or rabbit plasma in the presence of anticoagulant (citrate or heparin). Coagulase-negative staphylococci (CNS) used to be thought as non-pathogenic, however, they have become a major source of hospital-acquired infections:

Staphylococcus epidermidis Staphylococcus saprophyticus

Coagulase test and CNS

Cytolytic exotoxins: staphylolysin and leukocidin

Attack mammalian cell membranes, cause abscess and tissue necrosis. Often referred to as hemolysins.

Staphylolysins:

Four types: , , and

Staphylolysin , and can lyse erythrocytes (the basis for hemolytic reaction); toxic to many other cells such as white blood cells and muscle cells

Staphylolysin : close to leukocidin.

Leukocidin: lyse macrophages and neutrophils.

Hemolysis testBacteria are grown on sheep blood agar plates (containing 5% sheep blood):

α- hemolytic reaction,partial hemolysis with a green coloration：

β- hemolytic reaction, complete hemolysis：

γ - hemolytic reaction, no hemolysis:

Staphylococcus aureusStreptococcus pyogenes

Staphylococcus epidermidis most strains Staphylococcus saprophyticus

Streptococcus pneumoniae

SuperantigensSuperantigens can bind both to class II MHC molecules (but not in the peptide cleft) and also to a relatively conserved region of the TCR βchain. This leads to non-specific activation of 2-20% of all T cells (vs. 0.01%), and massive unregulated cytokine release.

Superantigen exotoxins: enterotoxin, TSST-1 , and exfoliatin

Enterotoxin, 9 serotypes, responsible for staphylococcal food poisoning.

TSST-1, close to enterotoxin, cause toxic shock syndrome (TSS).

Exfoliatin, 2 serotypes, cause staphylococcal scalded skin syndrome (SSS).

DiagnosisPus

abscesses and superficial skin lesionsSputum

lower respiratory tract infectionsBlood

septicemia, pyemiaFood/feces or vomit

food poisoningMid-stream urine

urethritis

S. aureus CNS Streptococcus Neisseria

Gram staining ++ ++ + -

bacteria morphology

irregular irregular clustersclusters

irregular irregular clustersclusters

Chains or pairs

Kidney-shaped

diplococci

colony pigmentation

GoldenGolden white

mannitol fermentation

++ -

hemolysis test ββ-hemolytic-hemolytic γ -hemolytic

coagulase test positivepositive negative

agglutination test

Use serum samples from patients.

Treatment and preventionAntibiotics

MRSA refers to methicillin (甲氧苯青霉素 )-resistant Staphylococcus aureus, and most MRSA strains are also multiply drug resistant

Chromosomal mutationPlasmid-conferred

CNS, eg. Staphylococcus epidermidisBiofilm formation

Exotoxin neutralizing antibodies

No vaccines available currently