Samira Karimaei - Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Rahil Mashhadi - Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Akram Mirzaei - Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Roham Deyhimfar - Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Alireza Namazi Shabestari - Department of Geriatric Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran.Iran
Ramin Rahimnia - Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

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 ۵۶۳۷ (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 ۱μg/ml and ۲μg/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 ۳۳۰ and ۴۳۰ μg/ml of Nisin compared to the negative control. Only a high dose of Nisin induced high levels of interleukin-۶ (IL-۶) in ACHN cells. In contrast, low concentrations of Nisin in ۵۶۳۷ cells induced the secretion of high levels of IL-۶. In cell culture, Nisin inhibited the S.aureus-induced cytotoxicity and the release of IL-۶ 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 ۵۶۳۷ cells. In summary, the bioactivities of Nisin make it a promising candidate as a further antimicrobial agent for targeting S. aureus infections.

Antimicrobial peptide, Biofilm, inflammatory responses, Nisin