Staphylococcus spp. Infections

Coagulase-negative staphylococci are commensal and opportunistic pathogenic bacteria that commonly inhabit the skin, nasopharynx, and intestine. In the mouse, disease has been associated with Staphylococcus aureus and S.

Chronic suppurative inflammation. Staphylococ­cus aureus is often associated with chronic suppurative inflammation of skin adnexae, conjunctiva, periorbi­tal tissue, preputial glands, and regional lymph nodes. Euthymic mice, as well as urokinase plasminogen activator-deficient mice, may develop suppurative conjunctivitis, ophthalmitis, and periocular abscessa­tion, with involvement of regional lymph nodes. Ocu­lar lesions tend to occur in strains of mice that are prone to development of conjunctivitis or with ocular defects, such as BALB and B6 mice. Preputial gland inflammation and abscesses are sporadically common in male mice. Occasionally, deep visceral abscesses may also be found. Lymphadenitis and abscesses have botryomy- cotic-like features, characterized by necrotizing suppura­tive inflammation with a central core of necrotic neutrophils and colonies of Gram-positive bacteria surrounded by bright eosinophilic amorphous to fibrillar Splendore-Hoeppli material (Fig. 1.76). The authors have also observed botryomycotic abscesses involving bone and extending into the nasal cavity associated with foreign body periodontitis.

Furunculosis. Distorted vibrissal hair shaft growth and impaired T-cell function predispose athymic nude mice to staphylococcal furunculosis of the muzzle (Fig. 1.77). These mice frequently have suppurative lymphadenitis of the regional lymph nodes.

Ulcerative dermatitis. An important form of staph­ylococcal disease is ulcerative dermatitis in association with S. aureus or S. xylosus. Staphylococci produce an array of biologically active proteins, including

FIG. 1.77. Muzzle furunculosis in a nude mouse associated with Staphylococcus aureus infection.

hemolysins, nucleases, proteases, lipases, hyaluroni­dase, and collagenase, and many produce exotoxins, including exfoliative toxins, leukocidin, and several superantigens, particularly enterotoxin A, enterotoxin B, enterotoxin C, and toxic shock syndrome toxin-1. This armamentarium is important in understanding the pathogenesis of staphylococcal ulcerative derma­titis in mice (and rats), which is characterized by superficial colonization of bacteria on the surface of the skin, with underlying burn-like features.

Ulcerative dermatitis is quite common in young and aged B6, BALB/c, DBA/2, and C3H/He mice and their hybrids, as well as other strains and stocks of mice. Disease prevalence is linked to other predisposing factors, includ­ing behavioral idiosyncrasies and ectoparasite hyper­sensitivity. For example, B6 mice are prone to trichotillomania and frequently suffer from ulcerative dermatitis (Fig. 1.78). Superficial excoriation of the skin is followed by colonization with Staphylococcus, pruritus, and then development of progressive necrotizing dermatitis. The syndrome has been well studied in hairless DS-Nh mice infected with S. aureus. DS-Nh mice normally manifest excessive scratching behavior. When they are housed in a conventional environment, they develop erythema, excoriation, and erosion around their head and neck. When first introduced to the environment, the mice become colonized with several Staphylococcus species, but S. aureus gradually becomes the dominant skin commensal over time, with selection for S. aureus types that produce enterotoxin C.

FIG. 1.76. Cervical lymph node, illustrating the botryomycotic inflammatory response due to Staphylococcus aureus infection. There are bacterial colonies and central aggregates of eosinophilic material consistent with a Splendore-Hoeppli reaction.

FIG. 1.78. Ulcerative dermatitis in a B6 mouse associated with Staphylococcus aureus infection. Note that the ventral abdomen is bald due to trichotillomania, with ulcerative dermatitis on the side.

Staphylococcal ulcerative dermatitis is characterized by focal small to large chronic ulcerative lesions, often around the head and neck, but also on the trunk or base of the tail. In the tail form of disease, gangrene and sloughing of the tail may occur. Apparently, the location of the skin lesions is associated with the initiating cause of excoriation (ectoparasites, grooming, fighting, etc.).

FIG. 1.79. Skin from a mouse with ulcerative dermatitis. Note the coagulation necrosis of the epidermis and dermis with the presence of bacterial colonies on the surface.

epidermis and dermis, which can extend to the subcutis and panniculus carnosis. The lesions are reminiscent of 1st, 2nd, or 3rd degree burns, which implicate the toxins elaborated by the Staphylococcus colonizing the surface of the lesions. Varying degrees of leukocytic infiltration and granulation are also present. The chronic lesions of Staphyloccal disease result in acceleration of multi- systemic amyloidosis and splenomegaly, with marked extramedullary myelopoiesis in liver and spleen. Plas- macytosis is present in regional lymph nodes. Scaly skin disease in nude mice, similar to the disease caused by C. bovis, has been associated with S. xylosus. However, lesions were more inflammatory and included foci of epidermal ulceration and pustule formation.

Diagnosis

An etiologic diagnosis requires isolation and speciation, but factors that predispose to susceptibility should be investigated, including immune status, strain-related behavior patterns, ectoparasitism, and ectoparasite- related hypersensitivity. Differential diagnoses include abscessation due to other bacterial infections and strep­tococcal necrotizing dermatitis. Amputation of the tail secondary to Staphylococcus-related dry gangrene must be differentiated from mousepox and tail lesions in mice infected with Mycobacterium chelonae.