Functional characterization and safety evaluation of an airway commensal Staphylococcus epidermidis HK 95

The airway epithelium plays a central role in maintaining respiratory homeostasis, and increasing evidence suggests that resident commensal bacteria contribute to airway protection through host-microbe interactions. However, the functional roles of individual airway commensals remain poorly defined. Here, we aimed to isolate and functionally characterize an airway commensal Staphylococcus epidermidis strain and to determine its influence on airway function as well as its safety profile.

An airway commensal S. epidermidis strain, designated HK 95, was isolated and characterized using a combination of in vivo, in vitro, and genomic approaches. Airway functional responses were evaluated in mice and guinea pigs using citric acid-induced acute cough, phenol red expectoration, and bronchoconstriction models. Safety assessments included cytotoxicity, hemolysis, antibiotic susceptibility testing, and evaluation in mice, integrating relative organ weight indices, longitudinal body weight assessment, and hematological profiling. Whole-genome sequencing and bioinformatic annotation were performed to assess taxonomic identity and safety-related genomic features.

Administration of S. epidermidis HK 95 significantly attenuated citric acid-induced airway irritation, as evidenced by reduced cough frequency and prolonged response latency in both mice and guinea pigs. In addition, S. epidermidis HK 95 enhanced tracheal secretion in mice, indicating improved airway secretory function, and significantly prolonged preconvulsive time in a guinea pig bronchoconstriction model, suggesting a protective effect on airway responsiveness. Comprehensive safety evaluations demonstrated that S. epidermidis HK 95 was non-haemolytic, exhibited a non-multidrug-resistant antibiotic susceptibility profile, and well tolerated following administration in mice, with no significant adverse effects or organ abnormalities. Whole-genome sequencing confirmed its taxonomic identity as S. epidermidis and did not identify genetic determinants associated with classical staphylococcal toxins or overt pathogenicity.

These findings demonstrate that the airway commensal S. epidermidis HK 95 exerts protective effects on airway physiological responses while maintaining a favorable safety profile. This study extends current understanding of airway commensal bacteria beyond compositional associations and supports a functional role for S. epidermidis in maintaining airway physiological homeostasis. These results provide a foundation for future studies exploring host-microbe interactions in the airway and the potential development of commensal-based airway interventions.