Nisin J, a Novel Natural Nisin Variant, Is Produced by Staphylococcus capitis Sourced from the Human Skin Microbiota.

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.

Protecting the outside: biological tools to manipulate the skin microbiota.

Interest surrounding the role that skin microbes play in various aspects of human health has recently experienced a timely surge, particularly among researchers, clinicians and consumer-focused industries. The world is now approaching a post-antibiotic era where conventional antibacterial therapeutics have shown a loss in effectiveness due to overuse, leading to the looming antibiotic resistance crisis. The increasing threat posed by antibiotic resistance is compounded by an inadequate discovery rate of new antibiotics and has, in turn, resulted in global interest for alternative solutions. Recent studies have demonstrated that imbalances in skin microbiota are associated with assorted skin diseases and infections. Specifically, restoration of this ecosystem imbalance results in an alleviation of symptoms, achieved simply by applying bacteria normally found in abundance on healthy skin to the skin of those deficient in beneficial bacteria. The aim of this review is to discuss the currently available literature on biological tools that have the potential to manipulate the skin microbiota, with particular focus on bacteriocins, phage therapy, antibiotics, probiotics and targets of the gut-skin axis. This review will also address how the skin microbiota protects humans from invading pathogens in the external environment while discussing novel strategies to manipulate the skin microbiota to avoid and/or treat various disease states.

Human skin microbiota is a rich source of bacteriocin-producing staphylococci that kill human pathogens.

The demand for novel antimicrobial therapies due to the threat posed by antimicrobial resistance has resulted in a growing interest in the protective role of our skin bacteria and the importance of competition among bacteria on the skin. A survey of the cultivable bacteria on human skin was undertaken to identify the capacity of the skin microbiota to produce bacteriocins with activity against skin pathogens. Twenty-one bacteriocins produced by bacteria isolated from seven sites on the human body of each subject exhibited inhibition spectra ranging from broad to narrow range, inhibiting many Gram-positive bacteria, including opportunistic skin pathogens such as Propionibacterium acnes (recently renamed Cutibacterium acnes), Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA). Sequencing indicated that the antimicrobial-producing isolates were predominately species/strains of the Staphylococcus genus. Colony mass spectrometry revealed peptide masses that do not correspond to known bacteriocins. In an era where antibiotic resistance is of major concern, the inhibitory effect of novel bacteriocins from the bacteria of skin origin demonstrates the antimicrobial potential that could be harnessed from within the human skin microbiota.