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 antibiotic-resistant 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 structured-illumination 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.

Highlights

  • The commensal bacterium Staphylococcus aureus colonizes the nasal cavity of about one third of the human population and is a leading cause of bacterial infections with disease manifestations ranging from superficial skin infections to life-threatening invasive disease (van Belkum, 2006)

  • We find very little variation in nisin Minimal inhibitory concentration (MIC) values for methicillinsensitive S. aureus (MSSA) and MRSA strains, suggesting that the SSCmec resistance determinant harbored by MRSA strains does not change susceptibility to nisin

  • We here show that exposure to nisin causes membrane depolarization and rapid killing of the JE2 community-acquired MRSA (CA-MRSA) model strain belonging to the fast spreading and highly virulent USA300 clone

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Summary

Introduction

The commensal bacterium Staphylococcus aureus colonizes the nasal cavity of about one third of the human population and is a leading cause of bacterial infections with disease manifestations ranging from superficial skin infections to life-threatening invasive disease (van Belkum, 2006). Effective treatment is hampered by the rapid spread of methicillin-resistant S. aureus. Nisin Activity Toward S. aureus (MRSA) that have acquired resistance to virtually all members of the β-lactam class of antibiotics (Vestergaard et al, 2019). Central to the pathogenicity of S. aureus are numerous secreted exotoxins, including the staphylococcal enterotoxins that are the causative agent of staphylococcal food poisoning, one of the most common causes of foodborne disease (Kadariya et al, 2014). It has been shown to work synergistically with conventional therapeutic drugs against MRSA and as an agent to control biofilm formation by S. aureus and other pathogens (Brumfitt et al, 2002; Dosler and Gerceker, 2011; Field et al, 2016; Shin et al, 2016; Mathur et al, 2018)

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