Antibacterial and Antibiofilm Activities of Nisin from Lactococcus lactis and Alteration of the Bacteria-Induced Pro-Inflammatory Responses on kidney and bladder tumor Cell Lines

Introduction: The emergence of superbugs puts the world into an antibiotic-resistance era, and antimicrobial peptides could solve this severe problem. The aim of this study was the in vitro evaluation of the bactericidal effects of the Nisin on Staphylococcus aureus, probable cytotoxic effects, and its impact on host-microbe interactions.Methods:  The minimal inhibitory concentration of Nisin was determined, and Nisin-induced cell toxicity was assessed by MTT assay. Then, the pro-inflammatory effects of Nisin on ACHN (kidney tumor cell line), and 5637 (bladder tumor cell line) cell lines were analyzed by ELISA (enzyme-linked immunoassay). Finally, the sensitivity of two biofilm-producing S. aureus to Nisin was evaluated in planktonic and biofilm-resident cells by crystal violet assay.Results: MIC for methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) was 1μg/ml and 2μg/ml, respectively. A low concentration of Nisin demonstrated no cytotoxic effects on studied cell lines. However, high cytotoxicity was found at the following concentrations of 330 and 430 μg/ml of Nisin compared to the negative control. Only a high dose of Nisin induced high levels of interleukin-6 (IL-6) in ACHN cells. In contrast, low concentrations of Nisin in 5637 cells induced the secretion of high levels of IL-6. In cell culture, Nisin inhibited the S.aureus-induced cytotoxicity and the release of IL-6 from kidney and bladder cell lines.Conclusions: Our results demonstrated that Nisin, efficiently inhibiting MRSA and MSSA strains, antagonized bacteria-induced inflammatory responses in ACHN and 5637 cells. In summary, the bioactivities of Nisin make it a promising candidate as a further antimicrobial agent for targeting S. aureus infections.