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.

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 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 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 (MRSA) and The gene order in the nisin J gene cluster () differs from that of other nisin variants in that it is lacking the nisin regulatory genes, , as well as the nisin immunity gene 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.

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).