Nisin G is a novel nisin variant produced by a gut-derived Streptococcus salivarius

Abstract

Fusobacterium nucleatum is an emerging human pathogen associated with a number of intestinal conditions including colorectal cancer (CRC) development. Screening for gut-derived strains that exhibit anti-F. nucleatum activity revealed Streptococcus salivarius DPC6487 as a strain of interest. Whole genome sequencing analysis of DPC6487 resulted in the identification of a gene predicted to encode a novel nisin 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. The cluster lacked an equivalent to the nisI immunity determinant. S. salivarius DPC6487 exhibited a narrower spectrum of activity compared to the nisin A producer, Lactococcus lactis NZ9700, when assessed through deferred antagonism-based assays. Such narrow spectrum activity is desirable as it is less likely to lead to collateral damage to gut commensals. Ultimately, this is the first report of a nisin variant produced by a representative of a species that is frequently a focus for probiotic development. The production of this bacteriocin by a gut-derived S. salivarius and its narrow spectrum activity against F. nucleatum indicates that this strain merits further attention to determine its potential for probiotic-related applications.

Nisin E Is a Novel Nisin Variant Produced by Multiple Streptococcus equinus Strains

“…We describe the production of a novel nisin E variant by two S. equinus strains, APC4007 and APC4008, that were isolated from unpasteurised sheep milk sampled from geographically separate locations in New Zealand; we then further describe the prevalence of this variant across the S. equinus pangenome using publicly available sequences. Nisin E described the following nisins: Z, U, F, Q, H, O1,2,3, and O4, P, J, G, and kunkecin A [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Streptococcal variants now compose 45% (U, H, P, G, E) of the natural nisin variants described, which may suggest an importance of their role in Streptococcus spp.…”

“…Nisin variants are typically broad spectrum in nature, inhibiting a range of Gram-positive species, but variants may possess different specific activities or be differentially produced. The recently described nisin G produced by S. salivarius DPC6487 was found to be selectively active against 9 of 23 tested bacteria (21 Gram-positive), including Gram negative Fusobacterium spp., whereas a nisin A producer inhibited all 21 Gram-positive isolates to varying degrees [ 27 ]. Similarly, nisin E inhibited 9 of the 40 Gram-positive bacteria screened, including Bacillus firmis DPC6349, Clostridioides spp., Lactobacillus spp., and Staphylococcus intermedius DSM20373 ( Table 2 ).…”

“…More recently, distantly related nisin J, nisin O (O123, and O4), and kunkecin A were identified from human skin, gut, and honeybee microbiota, and are produced by Staphylococcus capitis , Blautia obeum , and Apilactobacillus kunkeei FF30-6, respectively [ 20 , 21 , 22 ]. The genus Streptococcus has been a rich source of natural nisin variants, and species of diverse origin produce nisin variants U/U2, H, P, and most recently, G [ 23 , 24 , 25 , 26 , 27 ].…”

Effect of a bacteriocin-producing Streptococcus salivarius on the pathogen Fusobacterium nucleatum in a model of the human distal colon

“… 45 However, we recently reported a novel nisin variant designated as nisin G produced by S. salivarius DPC6487 with in vitro antimicrobial activity against F. nucleatum and other streptococci. 46 While these benefits show potential for targeting pathogenic bacteria associated with disease, several studies show additional potential benefits of S. salivarius , which may impact the gut, including anti-inflammatory properties 47 and maintaining microbial homeostasis. 25 …”

Nisin: Prerequisites and Prospects for Application in the Medical Field

“…Nisin is produced by gram-positive bacteria belonging to the genera Lactococcus, Streptococcus, Staphylococcus, and Blautia [4,5,[16][17][18][19]. Currently, at least twelve natural variants of nisin are known (Fig.…”