First evidence of production of the lantibiotic nisin P

Enriqueta Garcia-Gutierrez,Paul D Cotter,Gerhard Saalbach,Melinda J Mayer,Paula M O’Connor,Caitriona M Guinane,James W Hegarty,Arjan Narbad,Calum J Walsh

doi:10.1038/s41598-020-60623-0

Abstract

Nisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of two Streptococcus species, albeit with no confirmed evidence of production. Here we describe Streptococcus agalactiae DPC7040, a human faecal isolate, which exhibits antimicrobial activity against a panel of gut and food isolates by virtue of producing nisin P. Nisin P was purified, and its predicted structure was confirmed by nanoLC-MS/MS, with both the fully modified peptide and a variant without rings B and E being identified. Additionally, we compared its spectrum of inhibition and minimum inhibitory concentration (MIC) with that of nisin A and its antimicrobial effect in a faecal fermentation in comparison with nisin A and H. We found that its antimicrobial activity was less potent than nisin A and H, and we propose a link between this reduced activity and the peptide structure.

Highlights

Nisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of two Streptococcus species, albeit with no confirmed evidence of production
No annotation for LanB or LanC proteins was found in the genomes of the other stool S. agalactiae isolates, indicating that, among genome-sequenced strains, the nisin P operon is only present in S. agalactiae DPC7040
Highest probability (%) 100 7 — — 23 100 100. This is the first report of production of nisin P, a natural variant of nisin, originally predicted on the basis in silico of genomic analysis of other two streptococcal species[19,23]

Summary

Introduction

Nisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of two Streptococcus species, albeit with no confirmed evidence of production. Nisin Z is considered the first natural variant of nisin A; it differs in the presence of an asparagine amino acid in position 27 instead of a histidine residue[9]. This substitution has very little effect on antimicrobial activity, thermal and pH stability compared to nisin A, but affects the solubility of the molecule, with nisin Z being more soluble at neutral pH10. Nisin H, produced by Streptococcus hyointestinalis was the first variant isolated from a mammalian gastrointestinal (GI) tract (porcine)[15] and has five different amino acids at positions 1, 6, 18, 21 and 31. A faecal fermentation experiment was conducted to determine how a human faecal microbiota was affected by the presence of nisin A, H and P

Methods

Results

Conclusion