Research on the biotherapeutic value of the skin microbiome is relatively new, however, Atlantia Clinical Trials' research partner, Dr. Julie O'Sullivan (and colleagues) have been revolutionary in their approach to such research.
The human skin microbiota naturally harvests hundreds of bacterial species, which act as the bodies first line of defence/barrier against the outside world. The diversity and balance of bacterial communities is vital for skin health, many skin conditions are a result of imbalances occurring within the commensal microbiota. In terms of biotherapeutic value, there are a wide variety of biological tools that can manipulate the human skin microbiota, both directly and indirectly.
To provide context, bacteriocins are ribosomally synthesised, heat stable peptides which can kill other bacteria and are immune to their own bacteriocin, Dr. O’Sullivan outlines the significance of the skin microbiome in terms of therapeutic potential in this study. Similarly, Julie discuss’ a number of skin diseases, their characteristics and the causative organisms in recent academic literature in the below webinar.
Dr. O’Sullivan speaks briefly on her research area during her PHD, which involved a human skin screening study aimed to isolate antimicrobial producing bacteria. The population of the study was 20 and the age range was 18-65. Subjects swabbed themselves on 7 different body sites, Dr. O’Sullivan provides a more detailed discussion on what locations of the body was swabbed, and the methods used to analyse the swabs in the webinar. 90,000 colonies were screened for antimicrobial activity.
21 isolates were isolated and 16S RNA sequencing was carried out, identifying 5 main species (discussed in the webinar as well as the steps taken to characterize the strains). 3 strains were brought forward from the study, S. capitis and 2 S. hominis, all taken from one location of the body. This was followed by purification through Reversed Phase HPLC, and the fractions were collected from the HPLC for antimicrobial activity, and measures were taken to detect the masses of peptides in the active fractions, and a database search revealed that these masses did not correspond to any known masses. The producers were sent for whole genome sequencing to online programmes to locate bacterium operons
The initial screen of the S. capitis was promising due to the large zone of inhibition, it showed a broad range of antimicrobial activity against gram-positive pathogens, including Cutibacterium Acne among a range of different Staph and Strep species. Inputting the sequence to n online platform (discussed in the webinar), revealed an area of interest of 35 Amino acids that appeared to have a similar structure to that of wildtype nisin A. To provide an insight, nisin is the oldest characterised bacteriocin, and was the first ever FDA approved bacteriocin. nisin J has 9 amino acid changes when compared to wildtype nisin A, 8 amino acid substitutions, 6 of which are not present in any other natural nisin variant, and an extra amino acid and the C terminal region. This is the first report that a nisin variant has been isolated from a staph species, and the first time a nisin variant has been isolated from the human skin. Dr. O’Sullivan speaks further on her research identifying S. Hominis and its production of a novel antimicrobial ‘Homicin’.
It is a novel three-component lanthipeptide consisting of an alpha and two beta peptides, both peptides are required for antimicrobial activity. Homicin is also plasma encoded and displays a narrow-spectrum antimicrobial activity against GBS and Corynebacterium xerosis.
The 3 Staph hominis strains identified in both studies (Watkins, O’Sullivan, et al., ) produce Homicin, and it is believed that these human commensals have potential as live biotherapeutics for skin application. The three strains APC 2924, APC 2925, and APC 3675 have been patented.
Dr. Julie O’Sullivan of APC Microbiome Ireland works in the area of discovery and characterisation of novel bacteriocins (antimicrobial peptides) found within the human skin microbiota, in this online presentation Julie provides a unique insight to her post doctorate research with APC Microbiome Ireland.