Staphylococcus aureus Adaptation to the Skin in Health and Persistent/Recurrent Infections

Abstract

Staphylococcus aureus is a microorganism with an incredible capability to adapt to different niches within the human body. Approximately between 20 and 30% of the population is permanently but asymptomatically colonized with S. aureus in the nose, and another 30% may carry S. aureus intermittently. It has been established that nasal colonization is a risk factor for infection in other body sites, including mild to severe skin and soft tissue infections. The skin has distinct features that make it a hostile niche for many bacteria, therefore acting as a strong barrier against invading microorganisms. Healthy skin is desiccated; it has a low pH at the surface; the upper layer is constantly shed to remove attached bacteria; and several host antimicrobial peptides are produced. However, S. aureus is able to overcome these defenses and colonize this microenvironment. Moreover, this bacterium can very efficiently adapt to the stressors present in the skin under pathological conditions, as it occurs in patients with atopic dermatitis or suffering chronic wounds associated with diabetes. The focus of this manuscript is to revise the current knowledge concerning how S. aureus adapts to such diverse skin conditions causing persistent and recurrent infections.

Keywords: Staphylococcus aureus; adaptation; persistence.

Figure 1

Representation of the skin-cutaneous barrier in health and disease.

Figure 2

Genotypic diversity among nasal and skin S. aureus isolates in health and disease.

Figure 3

Regulation of S. aureus virulence factor expression in the skin during atopic dermatitis. An active Agr system is required for the initial development of atopic dermatitis. Once the disease has been established, the selection of agr-strains has been observed. The switch between an active and an inactive Agr system will lead to changes in the expression of virulence factors known to have a role in the pathogenesis of atopic dermatitis.

Figure 4

Regulation of S. aureus biofilm formation and detachment within the diabetic foot ulcer. Upon entry into the ulcer (Left panel) S. aureus encounters a hyperglycemic and alkaline microenvironment. The high levels of glucose under those pH conditions turn off the Agr system. Increased pH also activates SigB, which represses Agr. As a consequence of Agr downregulation and SigB activation, increased biofilm production is observed (middle panel). As the infection progresses, some individuals will turn back on Agr, likely due to the accumulation of AIPs and the heterogeneous conditions that the bacteria encounter within the biofilm. Agr activation leads to the expression of proteases and PSMs, which are known to be required for biofilm dispersion (right panel).