A prevalent constituent of the human skin flora is the coagulase-negative commensal Staphylococcus epidermidis^{1, 2}. This Gram-positive coccus predominantly inhabits the skin and mucosal membranes in areas such as the axillae, head, legs, arms, and nares. S. epidermidis plays a crucial role in maintaining a balanced microbiome within the human nasal cavity, where harmful pathogens like Staphylococcus aureus commonly establish colonization. There is ongoing discourse regarding whether S. epidermidis, through competition in nutritionally scarce environments like the human nose, may exhibit probiotic effects against formidable pathogens such as S. aureus^{2, 3}. Nevertheless, S. epidermidis is recognized as a significant causative agent of nosocomial infections under specific conditions⁴. Notably, S. epidermidis stands out as the primary source of infections associated with indwelling medical devices, including intravascular catheters and implants such as prosthetic joints^{1, 5, 6}. The high occurrence of these nosocomial infections is attributed to S. epidermidis’s ubiquitous presence on the human skin, increasing the likelihood of contamination during the insertion of medical devices⁷. Upon infection, S. epidermidis strains are capable of forming biofilms that shield them from antibiotics and host defense mechanisms, rendering S. epidermidis infections resistant and challenging to eliminate^{1, 7}. Often, removing the foreign material becomes necessary to combat the infection effectively. While S. epidermidis infections seldom lead to life-threatening conditions, their impact on patients and the public health system is substantial. In the United States alone, the annual economic burden of S. epidermidis vascular catheter-related bloodstream infections is estimated to be around $2 billion^{1, 6}. Besides biofilm formation, also other specific molecular determinants contribute to the pathogenicity of this particular pathogen, enabling immune evasion. Therefore, there is an urgent need for a more comprehensive understanding of S. epidermidis and its opportunistic characteristics to identify novel therapeutic strategies^{1, 7}.

One way to better understand an organism’s lifestyle and capabilities is the reconstruction and analysis of genome-scale metabolic models (GEMs). These models rely on the annotated genome sequence of the organism in question. Specifically, genes encoding proteins with metabolic significance are allocated to their respective reactions through gene-protein-reaction associations (GPRs). Within the resulting network, biochemical reactions establish connections between metabolites, with enzymatic activities guided by genes associated with these reactions. Such models enable the comprehension of an organism’s metabolism at a systemic level. Díaz Calvo et al. reconstructed the metabolic network of RP62A, a slime-producing and methicillin-resistant biofilm isolate⁸. However, the resulted model is available only upon request. Figure 1 summarizes the computational and experimental approach of this article. This work introduces iSep23, the first manually curated and experimentally validated GEM of S. epidermidis ATCC 12228. The model comprises 1,415 reactions, 1,051 metabolites, and 705 genes and is freely available from BioModels Database⁹ with the accession identifier MODEL2012220002. Moreover, it aligns with current community standards^{10, 11, 12} and modeling guidelines^{13, 14}. Semantic benchmarking was conducted utilizing the MEMOTE genome-scale metabolic model test suite¹⁵. Consequently, iSep23 upholds the Findable, Accessible, Interoperable, and Reusable (FAIR) data principles¹⁶, rendering it a valuable resource for subsequent research^{17, 18}. To assess the predictive capacity of the model, growth simulations in various media were compared against laboratory experiments. The model’s predictions regarding the utilization of diverse carbon sources were cross-referenced with experimental findings. Altogether, our model establishes a foundation for improved comprehension of the organism’s phenotypes and behavior under different nutritional conditions.