**5. Pathogenicity**

**Figure 1.** Pathogenic factors of *Staphylococcus aureus* with structural and secreted products both playing roles as virulence factors. (A) Surface and secreted proteins. (B and C) Cross sections of the cell envelope. TSST‐1, toxic shock syndrome toxin‐1. Source: With permission from the Massachusetts Medical Society. Copyright 1998 Massachusetts

> Endocarditis, osteomyelitis, septic arthritis, and prosthetic‐device and

Relapsing infections, cystic fibrosis, and syndromes as described above for

Invasive skin infections and necrotizing pneumonia (CA‐MRSA strains that cause these are often associated with PVL) abscesses (associated with capsular

Tissue destruction and metastatic

Food poisoning, toxic shock syndrome, scalded skin syndrome, bullous impetigo, and sepsis syndrome

catheter infections

attachment

polysaccharides)

infections

**Type of virulence factors Selected factorsa Associated clinical syndromes**

fibronectin‐binding proteins, collagen, and bone sialoprotein‐binding proteins)

intercellular adhesion), small‐colony variants,

Leukocidins (e.g., PVL and γ‐toxin), capsular polysaccharides (e.g., 5 and 8), protein A, CHIPS, Eap, and phenol‐soluble modulins

Proteases, lipases, nucleases, hyaluronate lyase, phospholipase C, and metalloproteases

Enterotoxins, toxic shock syndrome toxin‐1, exfoliative toxins A and B, α‐toxin, peptidoglycan, and lipoteichoic acid

Coagulase, ACME, and bacteriocin

Involved in attachment MSCRAMMs (e.g., clumping factors,

Involved in persistence Biofilm accumulation (e.g., polysaccharide

(elastase)

**Table 1.** Selected *Staphylococcus aureus* virulence factors.

and intracellular persistence

Medical Society.

120 Frontiers in Frontiers in Staphylococcus Aureus *Staphylococcus aureus*

Involved in evading/ destroying host defenses

Involved in tissue invasion/penetration

virulence

Involved in toxin‐mediated disease and/or sepsis

With poorly defined role in

Several mechanisms lead to blood stream infection with *S. aureus*. After adhering to tissues or prosthetic materials, *S. aureus* is capable of growing in various ways. It can evade host defenses and the activity of antibiotics by forming biofilms on host and prosthetic surfaces. Additionally, *S. aureus* may escape the defense mechanisms by surviving inside several types of cells (such as endothelial cells) as in the situation of bacteremia and endocarditis. Another mechanism of survival is that *S. aureus* can form small‐colony variants (SCVs) that can hide in host cells thus keeping them protected against defense mechanisms and leading to persistent and recurrent infection. The production of an antiphagocytic microcapsule is another method of defense escape used by *S. aureus* and can cause abscess formation. *S. aureus* can further halt host defenses by blunting neutrophil extravasation and chemotaxis to the infected area by producing chemotaxis inhibitory protein. Moreover, it produces leukocidins that destroy leucocytes by inflicting holes in the cell membrane.

Additional methods that help *S. aureus* in creating invasive blood stream infection exist and include the secretion of numerous enzymes that hydrolyzes tissues. This causes invasion, destruc‐ tion and further spread of the pathogen to distant organs via the blood stream. Septic shock can thus result through the activation of the individual's immune system and coagulation pathways.

Pathogenesis of *S. aureus* is also affected by regulation of the expression of virulence factors. It appears that expression of these factors in a coordinated manner reduces the metabolic demands of the pathogen. Thus, MSCRAMM proteins that get secreted early in the infectious process help the establishment of the infection in tissue sites, while the later production of toxins facilitates the spread of the infection. The accessory gene regulator (*agr*) is a quorum‐ sensing system that plays a critical role in the regulation of staphylococcal virulence.

Besides virulence factors of *S. aureus*, it appears that patients were sicker when they devel‐ oped an infection in the setting of negative colonization status. Noncarriers of the organism seem to have less protective immunity than those who are carriers. The formation of antibod‐ ies may also protect against the development of toxic shock syndrome.

Based on the above fact, *S. aureus* has many mechanisms to produce disease, namely bactere‐ mia, while evading host defenses.
