Staphylococcus epidermidis and its dual lifestyle in skin health and infection Original paper

What Was Reviewed?

This paper reviewed Staphylococcus epidermidis as a dominant member of the human skin microbiota and examined how this species occupies a dual role as both a beneficial commensal organism and an opportunistic pathogen. Rather than presenting a single experimental study, the authors synthesized molecular, immunological, microbiological, and clinical evidence to explain how strain-level diversity, host context, and microbial interactions determine whether S. epidermidis supports skin health or contributes to disease. The review focused on mechanisms of skin colonization, immune modulation, barrier maintenance, microbial competition, virulence factor expression, biofilm formation, and antibiotic resistance, with particular attention to translational relevance for dermatology and infectious disease practice.

Who Was Reviewed?

The review drew on data from studies involving healthy human skin, patients with inflammatory skin diseases such as atopic dermatitis and Netherton syndrome, hospitalized patients with implant-associated and bloodstream infections, and neonatal populations at risk for late-onset sepsis. It also incorporated evidence from animal models, including murine and porcine skin systems, to clarify immune–microbiota interactions and mechanisms of colonization and pathogenesis. Collectively, these populations allowed the authors to contrast commensal behavior on intact skin with pathogenic behavior in compromised hosts or disrupted barrier environments.

What Were the Most Important Findings?

The most important finding is that S. epidermidis does not behave uniformly across hosts or conditions; instead, its impact depends on strain-level heterogeneity and environmental context. On healthy skin, S. epidermidis actively contributes to immune education and barrier integrity. Specific strains prime neonatal immune tolerance through regulatory T cell recruitment, stimulate MAIT cells involved in tissue repair, and enhance adult barrier immunity via dendritic cell–T cell crosstalk. The bacterium produces bioactive molecules such as sphingomyelinase, trace amines, short-chain fatty acids, lipoteichoic acid, and phenol-soluble modulins that collectively increase ceramide production, accelerate wound healing, suppress excessive inflammation, and inhibit pathogens such as Staphylococcus aureus. These actions position S. epidermidis as a key driver of colonization resistance and skin homeostasis.

Conversely, the review highlights that certain S. epidermidis strains act as opportunistic pathogens. Major microbial associations include biofilm-forming lineages linked to implant infections, bloodstream infections, and neonatal sepsis, particularly sequence types adapted to hospital environments. Virulence factors such as the cysteine protease EcpA can degrade corneodesmosomes and antimicrobial peptides, worsening barrier dysfunction in atopic dermatitis and Netherton syndrome. The widespread carriage of antibiotic resistance genes, including methicillin resistance on mobile genetic elements, further elevates clinical risk. Importantly, the same genetic flexibility that supports commensal adaptation also enables pathogenic transitions.

What Are the Greatest Implications of This Review?

The central implication is that clinicians should move beyond viewing S. epidermidis as either harmless flora or mere contamination. Instead, it should be understood as a context-dependent organism with clinically meaningful strain-level effects. This has direct implications for interpreting microbiome data, managing device-related infections, and developing microbiome-based therapies. The review supports cautious but strategic exploration of S. epidermidis–based bacteriotherapies, emphasizing that strain selection and safety profiling are critical to avoid unintended pathogenic outcomes while leveraging immunomodulatory and antimicrobial benefits.