Nisin S, a Novel Nisin Variant Produced by Ligilactobacillus salivarius P1CEA3

Abstract

Recently, the food industry and the animal farming field have been working on different strategies to reduce the use of antibiotics in animal production. The use of probiotic producers of antimicrobial peptides (bacteriocins) is considered to be a potential solution to control bacterial infections and to reduce the use of antibiotics in animal production. In this study, Ligilactobacillus salivarius P1CEA3, isolated from the gastrointestinal tract (GIT) of pigs, was selected for its antagonistic activity against Gram-positive pathogens of relevance in swine production. Whole genome sequencing (WGS) of L. salivarius P1ACE3 revealed the existence of two gene clusters involved in bacteriocin production, one with genes encoding the class II bacteriocins salivaricin B (SalB) and Abp118, and a second cluster encoding a putative nisin variant. Colony MALDI-TOF MS determinations and a targeted proteomics combined with massive peptide analysis (LC-MS/MS) of the antimicrobial peptides encoded by L. salivarius P1CEA3 confirmed the production of a 3347 Da novel nisin variant, termed nisin S, but not the production of the bacteriocins SalB and Abp118, in the supernatants of the producer strain. This is the first report of a nisin variant encoded and produced by L. salivarius, a bacterial species specially recognized for its safety and probiotic potential.

Evaluation of Safety and Probiotic Traits from a Comprehensive Genome-Based In Silico Analysis of Ligilactobacillus salivarius P1CEA3, Isolated from Pigs and Producer of Nisin S

“…The assembled L. salivarius P1CEA3 genome, evaluated with the BAGEL v.4.0 and antiSMASH servers, indicated the existence of two distinct bacteriocin gene clusters in pMP1CEA3, one encoding the class II bacteriocins salivaricin B (SalB) and Abp118 (Abp118α and Abp118β), previously characterized in L. salivarius M6 and L. salivarius UCC118, respectively [ 58 , 59 ], and a second gene cluster encoding the lantibiotic nisin S [ 20 ]. The arrangement of genes within the nisin S gene cluster of pMP1CEA3 was nssABTCRKFEG , lacking the genes encoding a specific peptidase and an immunity protein, as compared to the nisin A gene cluster of Lactococcus lactis [ 20 ]. Previous results also demonstrated that although the abp118 structural genes of L. salivarius P1CEA3 were functional, deletions and mutations in genes related to its transport ( abpT and abpD ) and regulation ( abpK ) were preventing the synthesis and secretion of Abp118.…”

“…Ligilactobacillus salivarius P1CEA3 was isolated from the GIT of slaughtered pigs as previously described [ 20 ]. L. salivarius P1CEA3 was grown overnight at 37 °C in tryptic soy broth (TSB) (Oxoid Ltd., Basingstoke, UK) under anaerobic conditions using anaerobic jars with an AnaeroGen 3.5 l pack (Oxoid).…”

“…L. salivarius P1CEA3, a strain isolated from the GIT of pigs, has been previously identified as a bacteriocin-producing strain with a broad and strong antimicrobial activity against different pathogens including Streptococcus suis , other Gram-positive bacteria and Escherichia coli . The antimicrobial activity of L. salivarius P1CEA3 is mainly due to the production of the lantibiotic nisin S, the first fully characterized nisin variant produced by L. salivarius [ 20 ], which is a bacterial species recognized for its safety and probiotic potential. The present work aims to study the identification of probiotic and safety traits from a comprehensive genome-based in silico analysis of L. salivarius P1CEA3, and its potential in promoting the GI health in pigs.…”

Activity of Gut-Derived Nisin-like Lantibiotics against Human Gut Pathogens and Commensals

“…However, how nisin and nisin-like lantibiotics might impact the human gut microbiome has not been elucidated, nor has the presence of nisin-like compounds in the human gut microbiome been investigated in detail. The recent discovery of blauticin and nisin analogs clearly indicates that nisin-like molecules are encoded in the human microbiome, ,,, with other analogs detected in the microbiome of other mammals. , To first explore the biosynthetic potential of the gut microbiome for lantibiotic production, we systematically performed bioinformatic mining with RODEO for nisin-like lantibiotics derived from gut bacterial genomes. Subsequent filtering, multiple sequence alignment, and manual curation discovered six gut-derived nisin-like lantibiotics, four of which were not reported previously.…”

Rombocin, a Short Stable Natural Nisin Variant, Displays Selective Antimicrobial Activity against Listeria monocytogenes and Employs a Dual Mode of Action to Kill Target Bacterial Strains

“…Conventionally, culture-based techniques have been used to discover natural variants of nisin and other new bacteriocins ( Figure 1 ). 11 However, these techniques have limitations, which include laborious processes, low bacteriocin production under standard laboratory culturing conditions, and an increasing probability of rediscovering already known bacteriocins. To overcome these challenges, genome-guided methods that detect biosynthetic gene clusters (BGCs) that may encode novel nisin variants can be applied due to their numerous advantages.…”