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. 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.