A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiome

ABSTRACT Fusobacterium nucleatum is a human pathogen associated with intestinal conditions including colorectal cancer. Screening for gut-derived strains that exhibit anti-F. nucleatum activity in vitro revealed Streptococcus salivarius DPC6487 as a strain of interest. Whole-genome sequencing of S....

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Main Authors: Garreth W. Lawrence, Enriqueta Garcia-Gutierrez, A. Kate O’Mahony, Calum J. Walsh, Paula M. O'Connor, Máire Begley, Caitriona M. Guinane, Paul D. Cotter
Format: Article
Language:English
Published: American Society for Microbiology 2025-02-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.01573-24
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author Garreth W. Lawrence
Enriqueta Garcia-Gutierrez
A. Kate O’Mahony
Calum J. Walsh
Paula M. O'Connor
Máire Begley
Caitriona M. Guinane
Paul D. Cotter
author_facet Garreth W. Lawrence
Enriqueta Garcia-Gutierrez
A. Kate O’Mahony
Calum J. Walsh
Paula M. O'Connor
Máire Begley
Caitriona M. Guinane
Paul D. Cotter
author_sort Garreth W. Lawrence
collection DOAJ
description ABSTRACT Fusobacterium nucleatum is a human pathogen associated with intestinal conditions including colorectal cancer. Screening for gut-derived strains that exhibit anti-F. nucleatum activity in vitro revealed Streptococcus salivarius DPC6487 as a strain of interest. Whole-genome sequencing of S. salivarius DPC6487 identified a nisin operon with a novel structural variant designated nisin G. The structural nisin G peptide differs from the prototypical nisin A with respect to seven amino acids (Ile4Tyr, Ala15Val, Gly18Ala, Asn20His, Met21Leu, His27Asn, and His31Ile), including differences that have not previously been associated with a natural nisin variant. The nisin G gene cluster consists of nsgGEFABTCPRK with transposases encoded between the nisin G structural gene (nsgA) and nsgF, notably lacking an equivalent to the nisI immunity determinant. S. salivarius DPC6487 exhibited a narrower spectrum of activity in vitro compared to the nisin A-producing Lactococcus lactis NZ9700. Nisin G-producing S. salivarius DPC6487 demonstrated the ability to control F. nucleatum DSM15643 in an ex vivo model colonic environment while exerting minimal impact on the surrounding microbiota. The production of this bacteriocin by a gut-derived S. salivarius, its narrow-spectrum activity, and its anti-F. nucleatum activity in a model colonic environment indicates that this strain merits further attention with a view to harnessing its probiotic potential.IMPORTANCEFusobacterium nucleatum is a human pathogen associated with intestinal conditions, including colorectal cancer, making it a potentially important therapeutic target. Bacteriocin-producing probiotic bacteria demonstrate the potential to target disease-associated taxa in situ in the gut. A gut-derived strain Streptococcus salivarius DPC6487 was found to demonstrate anti-F. nucleatum activity, which was attributable to a gene encoding a novel nisin variant designated nisin G. Nisin G-producing S. salivarius DPC6487 demonstrated the ability to control an infection of F. nucleatum in a simulated model of the human distal colon while exerting minimal impact on the surrounding microbiota. Here, we describe this nisin variant produced by S. salivarius, a species that is frequently a focus for probiotic development. The production of nisin G by a gut-derived S. salivarius, its narrow-spectrum activity against F. nucleatum, and its anti-F. nucleatum activity in a model colonic environment warrants further research to determine its probiotic-related applications.
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spelling doaj-art-fd25647f1c6e45dab1a81420568b63902025-02-05T14:00:48ZengAmerican Society for MicrobiologymBio2150-75112025-02-0116210.1128/mbio.01573-24A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiomeGarreth W. Lawrence0Enriqueta Garcia-Gutierrez1A. Kate O’Mahony2Calum J. Walsh3Paula M. O'Connor4Máire Begley5Caitriona M. Guinane6Paul D. Cotter7Department of Biological Sciences, Munster Technological University, Cork, IrelandTeagasc Food Research Centre, Cork, IrelandTeagasc Food Research Centre, Cork, IrelandAPC Microbiome Ireland, Cork, IrelandTeagasc Food Research Centre, Cork, IrelandDepartment of Biological Sciences, Munster Technological University, Cork, IrelandDepartment of Biological Sciences, Munster Technological University, Cork, IrelandTeagasc Food Research Centre, Cork, IrelandABSTRACT Fusobacterium nucleatum is a human pathogen associated with intestinal conditions including colorectal cancer. Screening for gut-derived strains that exhibit anti-F. nucleatum activity in vitro revealed Streptococcus salivarius DPC6487 as a strain of interest. Whole-genome sequencing of S. salivarius DPC6487 identified a nisin operon with a novel structural variant designated nisin G. The structural nisin G peptide differs from the prototypical nisin A with respect to seven amino acids (Ile4Tyr, Ala15Val, Gly18Ala, Asn20His, Met21Leu, His27Asn, and His31Ile), including differences that have not previously been associated with a natural nisin variant. The nisin G gene cluster consists of nsgGEFABTCPRK with transposases encoded between the nisin G structural gene (nsgA) and nsgF, notably lacking an equivalent to the nisI immunity determinant. S. salivarius DPC6487 exhibited a narrower spectrum of activity in vitro compared to the nisin A-producing Lactococcus lactis NZ9700. Nisin G-producing S. salivarius DPC6487 demonstrated the ability to control F. nucleatum DSM15643 in an ex vivo model colonic environment while exerting minimal impact on the surrounding microbiota. The production of this bacteriocin by a gut-derived S. salivarius, its narrow-spectrum activity, and its anti-F. nucleatum activity in a model colonic environment indicates that this strain merits further attention with a view to harnessing its probiotic potential.IMPORTANCEFusobacterium nucleatum is a human pathogen associated with intestinal conditions, including colorectal cancer, making it a potentially important therapeutic target. Bacteriocin-producing probiotic bacteria demonstrate the potential to target disease-associated taxa in situ in the gut. A gut-derived strain Streptococcus salivarius DPC6487 was found to demonstrate anti-F. nucleatum activity, which was attributable to a gene encoding a novel nisin variant designated nisin G. Nisin G-producing S. salivarius DPC6487 demonstrated the ability to control an infection of F. nucleatum in a simulated model of the human distal colon while exerting minimal impact on the surrounding microbiota. Here, we describe this nisin variant produced by S. salivarius, a species that is frequently a focus for probiotic development. The production of nisin G by a gut-derived S. salivarius, its narrow-spectrum activity against F. nucleatum, and its anti-F. nucleatum activity in a model colonic environment warrants further research to determine its probiotic-related applications.https://journals.asm.org/doi/10.1128/mbio.01573-24nisinbacteriocinantimicrobialcolorectal cancerStreptococcus salivariusFusobacterium nucleatum
spellingShingle Garreth W. Lawrence
Enriqueta Garcia-Gutierrez
A. Kate O’Mahony
Calum J. Walsh
Paula M. O'Connor
Máire Begley
Caitriona M. Guinane
Paul D. Cotter
A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiome
mBio
nisin
bacteriocin
antimicrobial
colorectal cancer
Streptococcus salivarius
Fusobacterium nucleatum
title A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiome
title_full A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiome
title_fullStr A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiome
title_full_unstemmed A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiome
title_short A gut-derived Streptococcus salivarius produces the novel nisin variant designated nisin G and inhibits Fusobacterium nucleatum in a model of the human distal colon microbiome
title_sort gut derived streptococcus salivarius produces the novel nisin variant designated nisin g and inhibits fusobacterium nucleatum in a model of the human distal colon microbiome
topic nisin
bacteriocin
antimicrobial
colorectal cancer
Streptococcus salivarius
Fusobacterium nucleatum
url https://journals.asm.org/doi/10.1128/mbio.01573-24
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