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bioRxiv · 10.1101/2022.02.15.480493

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

Lawrence, G. W.·Garcia-Gutierrez, E.·Walsh, C. J.·O'Connor, P. M.·Begley, M.·Cotter, P. D.·Guinane, C. M.
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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.

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Lawrence, G. W., Garcia-Gutierrez, E., Walsh, C. J., O'Connor, P. M., Begley, M., Cotter, P. D., Guinane, C. M.. 2022-02-15. Nisin G is a novel nisin variant produced by a gut-derived Streptococcus salivarius. https://doi.org/10.1101/2022.02.15.480493

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