Diseases and Pathogenesis

Staphylococci may be transient contaminants, short-term replicating residents, or long-termcolonizers of the skin of mammals. Most that cause infection do so when the skin or mucous membranes are compromised in some way. Infections by S. aureus often begin at some breach in the epithelial barrier, whether keratinized, mucosal, or conjunctival, and establishment of infection is facilitated by foreign bodies, such as catheters, sutures, or even debris.

Virulence of staphylococci for domestic animals is almost always multifactorial, but interaction with animal hosts usually includes a few common steps. They produce microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), which comprise the main adhesins of the organism and include collagen-binding protein, fibronectin-binding proteins, fibrinogen-binding protein, elastin-binding protein, clumping factor, and the matrix adhesin factor. As many as 12 other surface proteins may contain membrane anchor domains and potentially qualify as MSCRAMMs. Roles in virulence have been postulated but not confirmed for infections of domestic animals.

Staphylococci are killed by neutrophils, so many of their virulence attributes are focused upon avoiding phagocytosis or intracellular killing. This is mediated in large part by production of capsules and protein A. Capsules, produced in 12 immunotypes, are antiphagocytic and those of type 1 are associated with enhanced virulence. Those strains not producing a type 1 macrocapsule may produce a polysaccharide microcapsule (for example, strains from mastitis); nonencapsulated strains are substantially more susceptible to phagocytosis and, in bovine mastitis and other in vivo models, less virulent. Protein A, which is found on the surface of the vast majority of strains of S. aureus, binds immunoglobulins by their Fc portion, limiting the degree of opsonization for phagocytosis. Mutants have reduced virulence in some in vivo systems. In a similar vein, teichoic acids and peptidoglycan fragments may serve as decomplementation antigens, exhausting in free solution the supply of complement components that would ordinarily be available for bacterial surface deposition (and thus opsonization). There are clearly two sides to this bacterial approach in host interaction: peptidoglycan interaction with host factors leads to complement activation (by classical or alternate pathways) and neutrophil chemotaxis.

Coagulase activates thrombin, with subsequent conversion of fibrinogen to fibrin. Some staphylococci produce coagulase (S. aureus, Staphylococcus intermedius, Staphylococcus schlieferi ssp. coagulans, and Staphylococcus delphini), while mostdo not; coagulase production by Staphylococcus hyicus is variable. The dogma that coagulaseproduction distinguished pathogenic from non-pathogenic species held until coagulase-negative staphylococci (CoNS) were recognized as a major cause of wound infections and infections associated with foreign bodies including catheters, prosthetic heart valves, joint prostheses, and pacemaker electrodes; thus coagulase is no longer an exclusive indicator of pathogenicity. Coagulase mutants and parent strains are of equivalentvirulence in various animal models of infection; nonetheless, some speculate that the enzyme participates in the infectious process by walling off the site of infection (limiting leukocyte infiltration and protecting the organisms against phagocytosis) or cloaking staphylococci in host proteins and preventing recognition as nonself.

Intracellular survival and spread are mediated in large part by production of toxins. Membrane-active toxins, some of which are enzymes, pro-tect the organism against the host response and provide access to host-derived nutrients. Many of the approximately 30 extracellular proteins produced by S. aureus are plasmid encoded, providing an armada of potential virulence factors that varies from strain to strain (Table 4-3). A single bacterial product is rarely of overriding importance in development of disease. Alpha toxin subunits bind to cell membranes, oligomerize, and form pores, leading to necrosis. Prostaglandins and other inflammatory mediators are released from some target cells, and macrophage function is compromised. Systemic effects of alpha toxin are most pronounced on cardiac and central nervous system tissue. Most bovine isolates of S. aureus produce β-toxin, a sphingomyelinase that lyses susceptible cells by enzymatic degradation of phospholipids in the outer leaflet of the membrane. Its role in pathogenesis is less clearly understood, but it augments staphylococcal growth in vivo. Hyaluronidase is a putative virulence attribute that may contribute to spread of the organism in the host.

TABLE 4-3 Virulence Factors of Staphylococcus aureus

Staphylococcus aureus causes suppurative infections and septicemia (Figure 4-1) in all species, and a few examples are illustrative. Arthropod bite wounds in lambs and other animals may become infected, and these animals may also develop lameness and bacteremia. Abscesses form in kidney, liver, joints, and brain, and death is rapid. The organism may also be associated with ovine periorbital eczema.

FIGURE 4-1 Staphylococcal septicemia in a chinchilla.

(Courtesy Raymond E. Reed.)