The Effects of Continuous In Vivo Administration of Nisin on Staphylococcus aureus Infection and Immune Response in Mice

Mice were intraperitoneally infected with 2 × 10⁸ cfu Staphylococcus aureus Xen 36 and treated with 2,130 AU (arbitrary units) nisin (equivalent to 27.7 μg pure nisin), a class Ia lantibiotic, over 7 days. The metabolic activity of S. aureus Xen 36, concluded from changes in cell bioluminescence, declined for the first 3.5 h, but increased over the next 24 h and remained at this level for the remainder of the 7-day trial. Similar results were obtained with heat-inactivated (25 min at 121 °C) nisin, suggesting that the decline in metabolic activity of S. aureus Xen 36 cannot be attributed to the bacteriostatic activity of nisin. The decline in lymphocyte numbers in infected mice was of smaller magnitude after treatment with active nisin compared to inactive nisin, suggesting that active nisin limited the apoptosis of lymphocytes. The drastic increase in neutrophil versus lymphocyte (N:L) ratio observed in the presence of active nisin suggested that the decline in metabolic activity of S. aureus Xen 36 was due to an immune response triggered by the infection. Nisin, active or inactive, stimulated the activity of cytokines interleukin-6, interleukin-10 and tumour necrosis factor. However, the overall immune response triggered by both forms of nisin was too minute to trigger an abnormally high antigenic immune reaction.