Clearance of experimental cutaneous Staphylococcus aureus infections in mice

Abstract

Staphylococcal skin infections are quite common in human patients. These infections often clear spontaneously, but may also progress locally and/or disseminate to cause serious and sometimes fatal deep infections. The present studies were undertaken to examine the clearance phase of experimental cutaneous Staphylococcus aureus infections in a mouse model system. Previous work in this system has shown that staphylococci applied to the skin rapidly disseminate to the spleen and kidney. In the present experiments the bacteria were found to persist at the skin infection site at a time (8 days after inoculation) when they had disappeared from the spleen and kidney. Examination of the infected skin at earlier times revealed rapid (within 6 h) invasion into the stratum corneum, stratum Malpighii, and dermis, but subsequent redistribution of bacteria (at 1-2 days) to more superficial sites, particularly crusts located just above the skin surface. The crusts seen in these infections were of two distinct types, which were termed type 1 and type 2. Type 1 crusts appeared first, consisted of bacteria, inflammatory cells, and debris, and developed over an intact epidermis. Type 2 crusts arose from the process of dermal necrosis previously reported to take place at 2 days in this model system. In the latter situation the bacteria were not really cleared from the epidermis and dermis; rather those layers were transformed into a superficial crust that contained the bacteria. Deep hair follicle infections in the dermis were found in these infections, but they did not persist and did not seem to be a reservoir for organisms in the dermis. Resolution of these experimental infections appeared to involve redistribution of invading bacteria to more superficial locations in crusts above the skin surface, marked proliferation of the epidermis, loss of the bacteria-laden crusts from the skin, and eventual healing of the cutaneous damage.

Epicutaneous Model of Community-Acquired Staphylococcus aureus Skin Infections

“…However, established animal models of S. aureus SSTI are more representative of HA-MRSA infections, such as surgical site and wound infections. Other models of SSTI utilize methods that may be difficult to replicate with uniformity (24)(25)(26). In the present study, we sought to develop a murine model that accurately and consistently mimics CA-MRSA SSTI in humans and to characterize the host response against this type of infection using this model.…”

“…Previous animal models of Staphylococcus aureus SSTI, however, largely mimic wound and surgical site infections, more representative of hospital-acquired infections, and have utilized methods of infection that are not easy to reproduce from animal to animal with precision. Many of these methods include disruption of the skin, such as by tape stripping (24), abrasion with a needle (25), or incision with a scalpel (26), followed by inoculation of the injured skin. Other methods include intradermal injection of S. aureus (23) or of dextran beads coated in S. aureus (27).…”

Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation

“…Thus, searching for sun-blocking agents may be a basic step in the prevention of skin damage by UVB irradiation. UVB (290-320 nm) irradiation is known to be a major cause for the epidermal damage in human skin (3). Keratinocytes constitute for 90% of the cells found in the epidermis and are capable of producing cytokines in response to external stimuli (4).…”

Direct translocation of staphylococci from the skin surface to deep organs

“…Recently we have found in experimental cutaneous infections in mice that staphylococci regularly disseminate from skin to spleen and kidneys within 6–24 hrs [2,3]. Spread to deep organs occurred before significant cutaneous invasion and it seemed possible that a process other than bacteremia might be involved.…”