| Summary: | <i>Staphylococcus epidermidis</i> is a major nosocomial pathogen with a remarkable ability to adhere to the surfaces of indwelling medical devices and form biofilms. Unlike other nosocomial pathogens, the interaction of <i>S. epidermidis</i> with host factors has not been the focus of substantial research. This study aimed to assess the alterations in the antibiotic susceptibility and biofilm formation ability of <i>S. epidermidis</i> in the presence of host serum factors. <i>S. epidermidis</i> strain RP62A was cultured in a laboratory culture medium with or without human serum/plasma, and changes in antibiotic susceptibility, biofilm formation, and gene expression were evaluated. The data obtained revealed that exposure to host serum factors increased the susceptibility of <i>S. epidermidis</i> to glycopeptide antibiotics and was also detrimental to biofilm formation. Gene expression analysis revealed downregulation of both <i>dltA</i> and <i>fmtC</i> genes shortly after human serum/plasma exposure. The importance of transferrin-mediated iron sequestration as a host anti-biofilm strategy against <i>S. epidermidis</i> was also emphasized. We have demonstrated that serum factors play a pivotal role as part of the host’s anti-infective strategy against <i>S. epidermidis</i> infections, highlighting the importance of incorporating such factors during in vitro studies with this pathogen.
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