Antimicrobial resistance is becoming an increasingly big problem. Currently, antimicrobial resistance causes 700,000 deaths per year, which is predicted to keep on rising. A recent study by Rudd et al. painted a far bleaker picture, claiming that sepsis causes 11 million deaths a year, making it the leading cause of death worldwide.
Thus, the discovery and development of new alternative antimicrobial therapies are vital.
The human skin microbiome naturally harbors hundreds of diverse bacterial species, which represent part of the body’s first line of defense against the outside world. The diversity and balance of bacterial communities are vital for skin health, with many skin conditions resulting from imbalances occurring within the commensal of microbiota.
Presently, there are numerous alternative biological tools that can be used in place of antibiotics for the treatment of skin infections, including bacteriocins, bacteriophage, probiotics and prebiotics.
The commensal bacteria or microbiota on our skin is thought to contribute to host health, protecting the host against a range of infections, including wound healing and anti-cancer properties. In this respect, the production of antimicrobial compounds is likely to be one of the defense mechanisms of the host microbiota.
This article will examine the potential of bacteriocins as alternatives to antibiotics for treating skin infections.
What are bacteriocins?
Bacteriocins are ribosomally synthesized, heat-stable peptides which can kill other bacteria and are immune to their own bacteriocins. Bacteriocins are viable alternatives to antibiotics, and their production is considered a probiotic trait.
Bacteriocins may act as colonizing peptides, helping a producer become established in a niche, killing peptides, killing off competitors, or they may function as signaling peptides signaling to other bacteria and the immune system. The skin microbiome is essentially a reservoir for novel bacteriocins with therapeutic potentials.
Skin conditions associated with skin commensals:
- Impetigo: Blister-shiny or crusted lesions
- Atopic dermatitis: Red, itchy, dry skin patches
- Acne vulgaris: Whiteheads, blackheads, pimples, lesions or scars
- Psoriasis: Red patches of skin covered with thick silvery scales
Staphylococci are a dominant skin commensal, and lantibiotics are a class of bacteriocins. Known Staphylococcal lantibiotics include Gallidermin, Epidermin, Hominicin, Nukacin ISK-1, Nukacin KQU-131 and Capidermicin.
In order to function, lantibiotics inhibit cell wall synthesis by binding Lipid II, which results in the formation of pores in the cell membrane, thus leading to membrane destruction. They generally have a broad inhibition spectrum against Gram positive bacteria, except for Hominicin, which has a particularly narrow spectrum, inhibiting Staph aureus species.
Characterizing the bacteriocin producing bacteria
In order to screen the skin of 20 different people between the ages of 18 and 65, the subjects swabbed seven different body sites, including the retroauricular crease behind the ear, the belly button, between the toes, the side of the nose, etc.
The swabs were then serially diluted and placed onto a selective media - Mannitol Salt agar - and a non-selective media - Brain Heart Infusion. Colonies of varying morphology and size were isolated from both the non-selective and selective media.
They were screened for bacteriocin production via spot assays and well diffusion assays. According to the results, varying sizes of inhibition zones showed that different bacteria are more active – an indicator of different skin pathogens.
Phenotypically, the colony morphology, gram stain, catalase and coagulase were examined. Genotypically, 16S rRNA sequencing and pulse field gel electrophoresis were used to ‘fingerprint’ the bacteria. The bacteria were then further characterized by means of heat stability, protein sensitivity and cross immunity.
The spectrum of inhibition was carried out to see what the isolated skin pathogens/microbiota were able to inhibit. MALDI TOF mass spec was used to find out what masses of the peptides were produced, and whole-genome sequencing was carried out on a small number of strains.
After the initial screen, 21 isolates were isolated. 16S rRNA sequencing was then carried out, which led to five main species being identified, including Staph hominis, Staph warneri, Epidermidis, Staph simulans and Staphyloccocus Capsis. Pulse field gel electrophoresis was used to ensure that only genetically distinct strains were used. This narrowed down the number of strains brought forward.
The skin antimicrobial-producing isolates displayed inhibitory activity against many skin pathogens, including MRSA, Cutibacterium acnes, Staph aureus and Corynebacterium species. Staph Capitis, and two Staph hominis strains - all isolated from the toe webspace area - were brought forward. These bacteriocins were then purified.
For purification, the cultures were grown in one liter of broth and purified using reverse phase high performance liquid chromatography (HPLC). The fractions were collected from the HPLC and acid for antimicrobial activity. MALDI Toff mass spec was then carried out to detect the masses of peptides in the active fractions.
The database search reveals that these masses did not correspond to any known masses. The producers were sent for whole genome sequencing, and the sequences were submitted to BAGEL and antiSMASH - free online programs used to locate bacteriocin operons - the results were quite interesting.
The initial screen of the Staph capitis stream showed great promise. It displayed a broad range of antimicrobial activity against Gram positive pathogens, including cutibacterium acne and a range of different Staph and Strep species.
Inputting the sequence into a BAGEL revealed an area of interest of 35 amino acids with a similar primary structure to wildtype Nisin A. Nisin is the oldest characterized bacteriocin and the first FDA-approved bacteriocin.
Hominis, produced by Staphylococcus hominis, is another interesting bacteriocin. Homicin is produced by three Staph hominis strains. Homicin was isolated in two separate studies; Dr. Julie O’Sullivan’s skin screen study and a vaginal screening study carried out by Dr.Claire Watkins.
It was clear from the outset that the strains were different. There was a color difference in the cell extracts, they displayed different fingerprints from the pulse fields profiles, and the strains had different masses.
Homicin was assayed against a range of relevant pathogens and was found to have a relatively narrow spectrum activity, inhibiting group B Streptococci bacterium species. The three Staph hominis strains from both studies produce Homicin, and these human commensal strains have potential as live biotherapeutics for skin application.
What can the cosmetics industry take away?
Bacteriocins are naturally produced by skin microbiota. Suppose it is possible to optimize their purification so that the peptides appear in a powder form and can be added to a topical cream. In that case, they could be used to rectify the imbalances in skin microbiota, which are more often than not the cause of many skin infections and issues.
To conclude, antimicrobial resistance is a major problem. Our skin bacteria naturally produce bacteriocins that display inhibitor activity against various skin pathogens and human pathogens, demonstrating their huge biotherapeutic potential.
In an era where antibiotic resistance is of major concern, our work demonstrates the huge antimicrobial potential that can be harnessed from within the skin microbiota.
About Atlantia Clinical Trials
Atlantia Clinical Trials Ltd is a CRO that specializes in conducting studies in foods, beverages and supplements for companies world-wide that want to scientifically validate their functional ingredients to support an: EFSA (European Food Safety Authority) Health Claim; FDA (Food & Drug Administration) Structure Function Claim; or General Product Marketing Claim.
Atlantia works with world leading scientists (among the top cited 1% internationally, in the areas of digestive health and functional foods) at the: APC Microbiome Institute in University College Cork, Ireland; Teagasc, Moorepark, Ireland and recognized centers of excellence globally.
Atlantia runs and operates its own clinic sites and conducts all studies to ICH-GCP standard (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice). Its team includes physician experts in digestive health, mental health (psychological stress and cognition), cardiovascular health, sports performance, metabolic disease, bone health, immune health and healthy ageing. The clinical team also includes project managers, research nurses, nutritionists, certified sports trainers and lab researchers.
Atlantia manages all elements from protocol design, placebo manufacture, recruitment, and study execution, to sample and data analysis, statistics and report/dossier preparation to provide a service which is technically, scientifically and clinically superior.
The clinical studies cover a broad spectrum of functional food and beverage categories, such as dairy, cereal, probiotic, different protein forms, infant-specific foods, vitamins/minerals, plant or marine extracts and medical foods.
Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.