Nano-engineering the Antimicrobial Spectrum of Lantibiotics: Activity of Nisin against Gram Negative Bacteria

Marija Vukomanović,Boštjan Jančar,Samo Jeverica,Špela Kunej,Vojka Žunič,Danilo Suvorov,Rok Podlipec

doi:10.1038/s41598-017-04670-0

Marija Vukomanović, Boštjan Jančar + Show 5 more

Open Access

https://doi.org/10.1038/s41598-017-04670-0

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Abstract

Lantibiotics, bacteria-sourced antimicrobial peptides, are very good candidates for effective and safe food additives. Among them, nisin is already approved by the EU and FDA, and has been used in food preservation for the past 40 years. Now, there is a possibility and strong interest to extend its applicability to biomedicine for designing innovative alternatives to antibiotics. The main obstacle is, however, its naturally narrow spectrum of antimicrobial activity, focused on Gram positive bacteria. Here we demonstrate broadening nisin’s spectrum to Gram negative bacteria using a nano-engineering approach. After binding nisin molecules to the surface of gold nano-features, uniformly deposited on spherical carbon templates, we created a nanocomposite with a high density of positively charged groups. Before assembly, none of the components of the nanocomposite showed any activity against bacterial growth, which was changed after assembly in the form of the nanocomposite. For the first time we showed that this type of structure enables interactions capable of disintegrating the wall of Gram negative bacteria. As confirmed by the nisin model, the developed approach opens up new horizons for the use of lantibiotics in designing post-antibiotic drugs.

Highlights

The main obstacle to the application of lantibiotics in clinical practice is their short half-life in the blood
The outer membrane of Gram negative bacteria is disintegrated and the bacteria become susceptible[14]. Another approach is through purification of the substance by removing salts, organic milk-sourced residuals and regulation of the pH15, since it was observed that salts decrease the permeability of the outer membrane, which blocks the activity against Gram negative bacteria[16]
It was emphasized that the extraordinary properties of antimicrobial peptides, including lantibiotics, can be very effectively explored by the development of new technologies for their modifications, which will open up new ways for the re-initiation of their commercialization[17, 18]

Summary

Introduction

The main obstacle to the application of lantibiotics in clinical practice (including nisin as their representative) is their short half-life in the blood. Our work was driven by the hypothesis that a combination of the nano-architecture and the intensive positive charge provided by the high local density of nisin molecules will join in the destabilization of the outer membrane and the formation of the pores inside the rest of the bacterial membrane, which will enable the activity of nisin against Gram negative bacteria. In this way we planned to develop a new technology capable of inducing the destabilization of the bacterial wall and provide activity across a broad spectrum of bacterial strains without the need for pre-treatments or purification before use

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Conclusion