The bacteriocin enterocin EJ97s retains its antibacterial effect upon interaction with human serum albumin

AIMS: The aim of this study was to investigate the interaction between the anti-enterococcal bacteriocin enterocin EJ97s (EntEJ97s) and human serum albumin (HSA) as a step in the pre-clinical assessment of this bacteriocin. METHODS AND RESULTS: The interactions between EntEJ97s and HSA were investigated using steady-state fluorescence, nano differential scanning calorimetry, and nano isothermal titration calorimetry (nanoITC). The results show low to moderate affinity between EntEJ97s and HSA, with a stoichiometry of less than one EntEJ97s per HSA molecule. NanoITC competition experiments with competitive ligands indicated that the peptide interacts with both the Sudlow I site and the Sudlow II site, the two main drug-binding sites on HSA. Molecular modelling efforts corroborated the findings of an interaction in the vicinity of these sites. The antibacterial effect of the peptide was preserved in the presence of physiological and experimental concentrations of HSA, as indicated by minimum inhibitory concentration experiments and spot-on-lawn assays. CONCLUSIONS: Our results suggest that EntEJ97s interacts with HSA without compromising its antibacterial effect. These findings accentuate the potential of this bacteriocin for intravenous treatment.