Nisin Damages the Septal Membrane and Triggers DNA Condensation in Methicillin-Resistant Staphylococcus aureus

Abstract

Nisin is applied as a food preservative in processed foods and has the potential to be used synergistically with antibiotics for treatment of patients infected by antibioticresistant bacteria, such as methicillin-resistant Staphylococcus aureus. The present study explores the antimicrobial effect of nisin on S. aureus viability and membrane integrity and, for the first time, used super-resolution microscopy to study morphological changes induced in S. aureus cells exposed to nisin. The exposure of S. aureus to nisin caused membrane depolarization and rapid killing. Super-resolution structuredillumination microscopy and transmission electron microscopy confirmed that nisin damages the cellular membrane and causes lysis of cells. Strikingly, condensation of chromosomal DNA was observed in all cells exposed to nisin, a phenotype not previously reported for this compound. Moreover, cells exposed to nisin were significantly smaller than non-exposed cells indicating the emergence of cell shrinkage. The strong association of DNA condensation with nisin exposure indicates that nisin interferes with chromosome replication or segregation in S. aureus.

Application of Lactobacillus helveticus CNRZ 32 to Control the Microbial Contaminants in Cheese by Addition of Bacterial Extracts or by In Situ Production of Bioactive Metabolites

“…decreased the count of the gram positive Staphylococcus sciuri, while Escherichia coli, molds and yeasts were increased. The great activity of this bacteriocin; Nisin was recorded by many researchers [27][28][29][30][31]. The arising count of gram negative bacteria and mycotic growth may be organized by the nutritional competition among microbial populations [32].…”

Bio-Engineered Nisin with Increased Anti-Staphylococcus and Selectively Reduced Anti-Lactococcus Activity for Treatment of Bovine Mastitis

“…For example, recent molecular dynamics simulations combined with microbiological techniques provided valuable insights at the atomic level into the interactions of nisin and an improved nisin derivative in association with the nisin resistance protein [28]. Additionally, recent studies have revealed new inhibitory mechanisms for nisin where in addition to membrane depolarization and rapid killing of cells, S. aureus strains exposed to nisin exhibited strong condensation of DNA, impeding chromosomal replication or segregation and suggests that this DNA damage might be a crucial component in the killing mechanism of nisin in S. aureus [46].…”

Nisin activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus and risk of resistance acquisition

“…More recently, nisin has been pointed as a potential treatment strategy for COVID-19, due to the affinity to the same receptor used by Coronavirus to infect cells (Bhattacharya et al, 2021). Bacteriocins have also shown the potential to control antibiotic-resistant pathogens (Jensen et al, 2020;Okuda et al, 2013;l., 2014). In addition, bacteriocins generally show high stability, low toxicity, and broad and narrow spectrum of activity (Cotter, et al, 2013).…”