Pathogen-responsive delivery of Nisin

Nisin, a food preservative commonly used in dairy and meat products, would be more effective if it was kept protected within a delivery system and its release accelerated in response to food contamination. Thus, nisin would remain stable in food for longer and only target harmful microorganisms. To achieve this goal, we describe here the first example of pathogen-responsive polyion complex (PIC) nanoparticles that release nisin preferentially in the presence of hyaluronidase-producing foodborne pathogens such as Staphylococcus aureus. In brief, we used a simple electrostatic complexation method with hyaluronic acid as an enzyme-degradable encapsulating polymer to produce small, well-defined spherical nisin-loaded PIC nanoparticles with good encapsulation efficiencies. These nisin-HA PIC nanoparticles displayed good stability at high salt concentrations, while the release of nisin was accelerated by hyaluronidase during in vitro experiments. More importantly, these nisin-HA PIC nanoparticles showed a better inhibitory effect against hyaluronidase-producing S. aureus than Bacillus cereus, a non-hyaluronidase-producing control. Finally, we performed a controlled contamination experiment to evaluate if these pathogen-responsive nanoparticles prevented microbial growth in milk, a representative food matrix. Remarkably, these nisin-HA PIC nanoparticles showed the same inhibitory effect as free nisin against hyaluronidase-producing S. aureus while having a minimal impact on non-hyaluronidase-producing B. cereus. Altogether, our findings highlight the potential of pathogen-triggered nisin release, suggesting innovative avenues for optimizing the delivery of this food preservative.