Staphylococcus aureus: Basic characteristics

• • Cocci (spheres)
• • Grapelike clusters
• • 1 micrometer diameter
• • Nonmotile
• • Low G + C
• • Halotoerant
• • Catalase (+)
• • Oxidase (-)
Virulence factors
1) Adherence to Host Cell Proteins
• S. aureus cells express surface proteins that promote attachment to host proteins such as laminin
and fibronectin that form the extracellular matrix of epithelial and endothelial surfaces. Most
strains
express a fibrin/fibrinogen binding protein (clumping factor) which promotes attachment to blood
clots and traumatized tissue.
2) Invasion factor
• The invasion of host tissues by staphylococci apparently involves the production of a huge array of
extracellular proteins, some of which may occur also as cell-associated proteins.
a) Membrane-damaging toxins
• alpha toxin (alpha-hemolysin)
• It is expressed as a monomer that binds to the membrane of susceptible cells. Subunits then
oligomerize to form heptameric rings with a central pore through which cellular contents leak. In
humans, platelets and monocytes are particularly sensitive to alpha toxin.
• ß-toxin is a sphingomyelinase which damages membranes rich in this lipid. The
• classical test for ß-toxin is lysis of sheep erythrocytes. The majority of human
• isolates of S. aureus do not express ß-toxin. A lysogenic bacteriophage is known
• to encode the toxin.
• • Leukocidin is a multicomponent protein toxin produced as separate
components
• which act together to damage membranes. Leukocidin forms a hetero-oligomeric
• transmembrane pore composed of four LukF and four LukS subunits, thereby
• forming an octameric pore in the affected membrane. Leukocidin is hemolytic,
• but less so than alpha hemolysin.
• b) Coagulase and clumping factor
Coagulase is an extracellular protein which binds to prothrombin in the host to form a complex called
staphylothrombin. The protease activity characteristic of thrombin is activated in the complex, resulting in
the
conversion of fibrinogen to fibrin. Reacting with prothrombin leads to fibrin clotting. Thus, the bacteria could
protect themselves from phagocytic and immune defenses by causing localized clotting.
c) Staphylokinase
Many strains of S aureus express a plasminogen activator called staphylokinase. This factor lyses fibrin. The
genetic determinant is associated with lysogenic bacteriophages. A complex formed between staphylokinase
and
plasminogen activates plasmin-like proteolytic activity which causes dissolution of fibrin clots. Localized
fibrinolysis aids in bacterial spreading.
d) Other extracellular enzymes
S. aureus can express proteases, a lipase, a deoxyribonuclease (DNase) and a fatty acid modifying enzyme
(FAME). The first three provide nutrients for the bacteria. The FAME enzyme may have role in abscesses,
where it
could modify anti-bacterial lipids and prolong bacterial survival.
• 3) Avoidance of Host Defenses
S. aureus expresses a number of factors that have the potential to interfere with host
defense
mechanisms. This includes both structural and soluble elements of the bacterium.
Capsular Polysaccharide The majority of clinical isolates of S aureus express a surface
polysaccharide
of either serotype 5 or 8. This has been called a microcapsule because it can be visualized
only by
electron microscopy unlike the true capsules of some bacteria which are readily
visualized by light
microscopy.
Protein A Protein A is a surface protein of S. aureus which binds IgG molecules by their Fc
region. In
serum, the bacteria will bind IgG molecules in the wrong orientation on their surface,
which disrupts
opsonization and phagocytosis.
• 4) Exotoxins
• Some toxins damage the membranes of cells. Some lyse erythrocytes, causing
hemolysis.
• Leukocidin causes membrane damage to leukocytes, but is less hemolytic.
• Systemic release of alpha toxin causes septic shock, while enterotoxins and
TSST-1
are superantigens that may cause toxic shock.
• Staphylococcal enterotoxins cause emesis (vomiting) when ingested and the
bacterium is a leading cause of food poisoning (intoxication).
• The exfoliatin toxin causes scalded skin syndrome in neonates, which results in
widespread blistering and loss of the epidermis. There are two antigenically
distinct forms of the toxin, ETA and ETB. The toxins have esterase and protease
activity and apparently target a protein which is involved in maintaining the
integrity of the epidermis.
• 5) Superantigens: enterotoxins and toxic shock syndrome toxin
S. aureus secretes two types of toxins with superantigen activity, enterotoxins, of which there are
six antigenic types (named SE-A, B, C, D, E and G), and toxic shock syndrome toxin (TSST-1).
TSST-1 is expressed systemically and is the cause of toxic shock syndrome (TSS).
Enterotoxins cause diarrhea and vomiting when ingested and are responsible for staphylococcal
food poisoning. When expressed systemically, enterotoxins can also cause toxic shock syndrome
Superantigens stimulate T cells non-specifically without normal antigenic recognition. Up to one
in
five T cells may be activated, whereas only 1 in 10,000 are stimulated during a usual antigen
presentation. Cytokines are released in large amounts, causing the symptoms of TSS.
Superantigens
bind directly to class II major histocompatibility complexes of antigen-presenting cells outside the
conventional antigen-binding grove. This complex recognizes only the Vb element of the T cell
receptor. Thus any T cell with the appropriate Vb element can be stimulated, whereas normally,
antigen specificity is also required in binding.
• FIGURE: Superantigens and the non-specific stimulation of T cells. Superantigens bind
directly to class II major histocompatibility complexes (MHC II) of antigen-presenting
cells outside the normal antigen-binding groove. Up to one in five T cells may be
activated. Cytokines are released in large amounts, causing the symptoms of toxic
shock.
• 6) Cell Surface Factors: Capsule & Fibronectin-binding Proteins
• • S. aureus cell wall-associated virulence factors include capsular polysaccharides (CPs),
• staphyloxanthin (carotenoid pigment), and a group of proteins known as microbial
• surface components recognizing adhesive matrix molecules (MSCRAMMs).
• • The main function of capsules in staphylococcal virulence is to impede phagocytosis
• by neutrophils, but it has also been shown to enhance bacterial colonization and
• persistence on mucosal surfaces.
• • S. aureus pigment staphyloxanthin, also functions to resist killing by neutrophils.
• • MSCRAMMs, such as clumping factors (Clf), fibronectin-binding proteins (FnBP),
• collagen adhesion and protein A, play important roles in microbial adhesion to host
• proteins (i.e., fibronectin, fibrinogen and collagen) and establish the first step of an
• infection.
• 7) Secreted Factors: Lipases, Cytolysins, Superantigens & Proteases
• • In contrast to the protective and passive role of cell wall-associated
• virulence factors, secreted S. aureus virulence factors play active roles
• in disarming host immunity by disrupting host cells and tissues and
• interfering with the host immune system to release nutrients and
• facilitate bacteria dissemination. The secreted virulence factors are
• comprised of four main categories: superantigens, pore-forming
• toxins, various exoenzymes and miscellaneous proteins.
Table. Secreted Staphylococcus aureus virulence
factors.
Secreted virulence factor Putative function
Lipase Inactivate fatty acids
Hyaluronidase Degradation of hyaluronic acid

Serine proteases; cysteine proteases (including Inactivate neutrophil proteolytic activity; inactivate
staphopains); aureolysin antimicrobial peptides

Plasminogen activation; inactivate antimicrobial

Staphylokinase
peptides
Exfoliative toxins Act as serine proteases; activate T cells
Chemotaxis inhibitory protein of Staphylococccus
aureus; Inhibit complement
Staphylococcal inhibitor of complement
Staphylococcal superantigen-like proteins;
Inhibit complement C5 and IgA; inhibit neutrophil
extracellular
migration
adherence protein
• 8) Cytotoxins
• S. aureus secrete a large number of pore-forming toxins, including
cytolysins (α-, β-, γ-, and δ-toxins), leukocidin family (leukocidin,
LukD/E, LukM and PVL), and phenol-soluble modulins (PSMs).
Although
these toxins are structurally diverse and have various target specificity
(i.e., erythrocytes, leukocytes and epithelial cells), their function on
host cells is similar. They form pores in the membranes of target cells
and cause leakage (osmotic swelling) and inflammation of the cells at
low doses, and cell lysis at high doses.
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