carriage.

Genetic factors, perhaps involving bacterial adherence and immune

responses, are suggested by higher nasal carriage rates in white than blackskinned
individuals, by studies of fami lies and twins, by higher than normal rates in patients
with phe nylketonuria, by increased adherence in atopic eczema and by an
association of nasal carriage with human leukocyte antigen (HLA)DR3 [1114]. In
those susceptible to nasal colonization, the overall rate depends on the extent to
which the many transient carriers acquire the organism by contact with persistent
carriers. This at least partly underlies the increase in carriage rates follow ing
hospital admission [15], higher rates in urban than in rural areas [16] and variation
in carriage rates with age. High rates of nasal carriage in atopic eczema (79%) [17]
may partly derive from the heavy load of S. aureus on the skin, but increased
adhesion of the organism to nasal mucosal cells may be relevant [18]. As a primary
reservoir of S. aureus, nasal carriage has been identified as a major risk factor for
the subsequent development of com munityacquired and nosocomial infections.
Those patients on ambulatory peritoneal or haemodialysis, who carry S. aureus in
the nose, are much more likely to get infection of the exit sites, usually with the
same bacterial strain [15]. Patients with HIV infection and AIDSrelated diseases,
have higher carriage rates of S. aureus than those unaffected, even when
intravenous drug users are excluded among the HIVpositive individuals, and this is
a risk factor for the subsequent severe infection with S. aureus [19]. The underlying
mechanism for this is as yet unclear. Vari ous surface components of S. aureus, such
as teichoic acid, LTA, fibronectinbinding proteins, and type 5 and type 8 capsular
polysaccharides, have all been implicated as substances respon sible for, or
contributing to, binding of the organism in the nose [15]. However, not all have
been successfully confirmed. Intesti nal carriage of S. aureus is particularly common
among hospital ized patients, and this may be associated with transmission of the
organism to the skin. The organism was identified not only in the nose (45%), but
also in the stool (36%) of 71 hospitalized subjects [20]. The majority of these
patients were persistent stool carriers. Furthermore, swabs taken from
environmental surfaces, such as the bedside tables, showed contamination of these
surfaces too. Molecular typing of the organisms showed some of the isolates from
the nose and stool were clonally identical to those from the environmental sources
[20].

Staphylococcus aureus has the ability to produce numerous surface factors and
proteins that help it to survive and evade host immu nity. The most highly
characterized surface defence of S. aureus is protein A which is composed of five
homologous immunoglobu lin/antibody binding domains, each able to bind to the fc
region of antibodies and the fab region of the human VH3 family. This binding
inhibits the antibodies from fixing complement or direct ing macrophages which
results in disruption of opsonisation and phagocytosis. Higher levels of protein A are
more commonly associated with strains leading to persistent nasal colonization. S.
aureus synthesizes another protein called coagulase which trig gers the clotting
cascade leading to the production of a mesh of plasma proteins which effectively
surrounds the bacteria giving it an immunological cloak of disguise. The ability of S.
aureus to invade deep tissues is facilitated by the production of collagenases and
hyaluronidase. (bolognia)

Colonization by S. aureus may be transient or repre- sent a prolonged carrier state.

S. aureus produces many cellular components and extracellular products that may
contribute to its pathogenicity. Host factors such as immunosuppression,
glucocorticoid therapy, and atopy may play a major role in the pathogenesis of
staphylococcal infections. Preexisting tissue injury or inflammation (surgical wound,
burn, trauma, dermati- tis, retained foreign body) is of major importance in the
pathogenesis of staphylococcal disease. Some strains produce one or more
exoproteins, including the staphylococcal enterotoxins (SEA, SEB, SECn, SED, SEE,
SEG, SEH, and SEI), and the exfolia- tive toxins (ETA and ETB), TSS toxin-1 (TSST-1),
and leukocidin. These toxins have unique potent effects on immune cells and other
biologic effects as well, ulti- mately inhibiting host immune response. TSST-1 and
the staphylococcal enterotoxins are also known as pyrogenic toxin superantigens.
These molecules act by binding directly to constitutively expressed HLA-DR
molecules (major histocompat- ibility complex II) on antigen-presenting cells without
antigen processing. Although conventional antigens require recognition by all five
elements of the T-cell- receptor complex, superantigens require only the variable
region of the -chain. As a result, 5%30% of resting T cells may be activated,
whereas the nor- mal antigenic response is only 0.0001%0.01% of T cells.6
Nonspecific T-cell activation leads to massive systemic release of cytokines,
especially interleukin 2, interferon-, and tumor necrosis factor- from T cells and
interleukin 1 and tumor necrosis factor- from macrophages.7 Superantigen
stimulation of T cells also results in activation and expansion of lymphocytes
expressing specific T cell-receptor variable region of the -chain. They may activate
B cells, leading to high levels of immunoglobulin E (IgE) or autoantibodies.8 Also,
there is evidence that superantigens selectively induce cutaneous lymphocyte-
associated antigen on T cells, thereby homing them to the skin.8 There are
several other mechanisms by which S. aureus evades immune clearance.
Approximately 60% of S. aureus strains secrete the chemotaxis inhibitory protein of
Staphylococci, which inhibits neutrophil chemotaxis. Additionally, protein A,
staphylokinase, capsular polysaccharide, fibrinogen binding protein, and clumping
factor A all act to aid in avoidance of being opsonized and phagocytosed.
Staphylokinase and aureolysin bind and cleave antimicrobial peptides, respectively,
resulting in increased survival in vitro and probably in vivo. (Fitzpatrick)