Nisin J, a novel natural nisin variant, is produced by Staphylococcus capitis sourced from the human skin microbiota

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O'Sullivan, Julie N.
O'Connor, Paula M.
Rea, Mary C.
O'Sullivan, Orla
Walsh, Calum J.
Healy, Brian
Mathur, Harsh
Field, Des
Hill, Colin
Ross, R. Paul
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American Society for Microbiology
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The skin microbiota is thought to play a key role in host protection from infection. Nisin J is a novel nisin variant produced by Staphylococcus capitis APC 2923, a strain isolated from the toe web space area in a screening study performed on the human skin microbiota. Whole-genome sequencing and mass spectrometry of the purified peptide confirmed that S. capitis APC 2923 produces a 3,458-Da bacteriocin, designated nisin J, which exhibited antimicrobial activity against a range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Cutibacterium acnes The gene order in the nisin J gene cluster (nsjFEGBTCJP) differs from that of other nisin variants in that it is lacking the nisin regulatory genes, nisRK, as well as the nisin immunity gene nisI Nisin J has 9 amino acid changes compared to prototypical nisin A, with 8 amino acid substitutions, 6 of which are not present in other nisin variants (Ile4Lys, Met17Gln, Gly18Thr, Asn20Phe, Met21Ala, Ile30Gly, Val33His, and Lys34Thr), and an extra amino acid close to the C terminus, rendering nisin J the only nisin variant to contain 35 amino acids. This is the first report of a nisin variant produced by a Staphylococcus species and the first nisin producer isolated from human skin.IMPORTANCE This study describes the characterization of nisin J, the first example of a natural nisin variant, produced by a human skin isolate of staphylococcal origin. Nisin J displays inhibitory activity against a wide range of bacterial targets, including MRSA. This work demonstrates the potential of human commensals as a source for novel antimicrobials that could form part of the solution to antibiotic resistance across a broad range of bacterial pathogens.
Antimicrobial agents , Antimicrobial peptides , Antimicrobial structure , Bacteriocins , Microbiota , Natural antimicrobial products , Nisin , Skin microbiota
O’Sullivan, J. N., O’Connor, P. M., Rea, M. C., O’Sullivan, O., Walsh, C. J., Healy, B., Mathur, H., Field, D., Hill, C. and Ross, R. P. (2020) ‘Nisin J, a novel natural nisin variant, is produced by Staphylococcus capitis sourced from the human skin microbiota’, Journal of Bacteriology, 202(3), (15pp). doi: 10.1128/JB.00639-19