Nisin J, a Novel Natural Nisin Variant, Is Produced by Staphylococcus capitis Sourced from the Human Skin Microbiota.

Julie N O’Sullivan,Colin Hill,R Paul Ross,Des Field,Calum J Walsh,Mary C Rea,Orla O’Sullivan,Harsh Mathur,Paula M O’Connor,Brian Healy,George O’Toole

doi:10.1128/jb.00639-19

Abstract

The skin microbiota is thought to play a key role in host protection from infection. Nisin J is a novel nisin variant produced by Staphylococcus capitis APC 2923, a strain isolated from the toe web space area in a screening study performed on the human skin microbiota. Whole-genome sequencing and mass spectrometry of the purified peptide confirmed that S. capitis APC 2923 produces a 3,458-Da bacteriocin, designated nisin J, which exhibited antimicrobial activity against a range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Cutibacterium acnes The gene order in the nisin J gene cluster (nsjFEGBTCJP) differs from that of other nisin variants in that it is lacking the nisin regulatory genes, nisRK, as well as the nisin immunity gene nisI Nisin J has 9 amino acid changes compared to prototypical nisin A, with 8 amino acid substitutions, 6 of which are not present in other nisin variants (Ile4Lys, Met17Gln, Gly18Thr, Asn20Phe, Met21Ala, Ile30Gly, Val33His, and Lys34Thr), and an extra amino acid close to the C terminus, rendering nisin J the only nisin variant to contain 35 amino acids. This is the first report of a nisin variant produced by a Staphylococcus species and the first nisin producer isolated from human skin.IMPORTANCE This study describes the characterization of nisin J, the first example of a natural nisin variant, produced by a human skin isolate of staphylococcal origin. Nisin J displays inhibitory activity against a wide range of bacterial targets, including MRSA. This work demonstrates the potential of human commensals as a source for novel antimicrobials that could form part of the solution to antibiotic resistance across a broad range of bacterial pathogens.

Highlights

The skin microbiota is thought to play a key role in host protection from infection
Nisin J contains an extra amino acid at the C terminus, making nisin J the longest nisin variant identified to date (Fig. 1A)
Nisin J is a novel nisin variant and the first such variant reported from a Staphylococcus species

Summary

Introduction

Nisin J is a novel nisin variant produced by Staphylococcus capitis APC 2923, a strain isolated from the toe web space area in a screening study performed on the human skin microbiota. Genomic analysis of an S. capitis strain isolated from the skin of a human toe revealed the presence of gene clusters capable of encoding gallidermin, epidermin, and phenol soluble modulins, highlighting its potential to produce antimicrobial. Our group detected antimicrobial activity by a number of S. capitis strains isolated from different areas of the human skin [5] and highlighted the potential for S. capitis species to produce bacteriocins (small ribosomally synthesized peptides produced by a range of bacteria which kill other bacteria). Lantibiotics have been shown to possess activity against antibiotic-resistant targets such as vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) and may have the potential to mitigate the looming global AR crisis [26]

Methods

Results

Conclusion