Metabolic and regulatory adaptations of Staphylococcus epidermidis to host stresses

Staphylococcus epidermidis is a highly adapted commensal of the human skin. However, it can also cause severe infections by exploiting skin fissures to establish antibiotic-resistant biofilms on implanted medical devices, which may subsequently release bacteria into the bloodstream. Emerging studies increasingly highlight the critical role of metabolic status and regulatory mechanisms in governing biofilm formation and, consequently, the pathogenic potential of S. epidermidis. This review examines its metabolic adaptability across different environments, emphasizing how environmental factors such as nutrient availability, oxygen levels, pH, and temperature, shape central metabolic pathways. It covers sugar, amino acid, and fatty acid utilization, regulatory networks controlling respiration, fermentation, and polysaccharide intercellular adhesin (PIA)-mediated biofilm formation, and strategies for surviving host-derived oxidative and nitrosative stresses. Comparisons with S. aureus further reveal species-specific differences in metabolism, nutrient acquisition, and regulation. Altogether, the mechanistic insights provide a comprehensive overview of S. epidermidis physiology in both commensal and infection-associated contexts.