I’m not really a great fan of Twitter – I have an account, I scroll through it periodically on my phone when on the train but I never have anything really to say on it. Maybe that’s because I like talking and everything I have to say I cannot condense down to a 140 character Tweet.
However, on one recent long train journey I came across a Tweet for a new anti-eczema cream. This cream not only purported to treat eczema but also acne and rosacea and other skin irritations. I had a quick read through it but lodged it in my memory to research later.
Lo and behold, the following day the mother of a child with eczema came to clinic and brought forth the cream from her handbag. There was the usual story that none of the prescribed creams worked but this one really did and the child no longer needed any topical steroids either. I had to admit that the child’s eczema really was better, though not completely gone, and still required some topical steroid. We often attribute improvements in eczema to the improving weather in the Spring and Summer months or sometimes it just improves on its own as eczema does tend to wax and wane. I did, however, have to confess to the mother that I knew nothing of the cream and promised to look into it further.
What did my research show?
The cream contained an enzyme of a type called an endolysin.
What is an endolysin?
It is an enzyme used by certain viruses called bacteriophages. These are viruses that infect bacteria. Endolysins dissolve a part of the bacterial cell wall called the peptidoglycan cell layer, an essential part of the virus life cycle.
Whoa! What’s a peptidoglycan cell layer?
Bacteria have a cell wall which is composed of peptidoglycans which are largely sugars and proteins which form a mesh around the cell. This mesh-like layer gives strength to the cell wall counteracting the pressure from the fluid-like centre of the bacterium. In essence, the cell wall holds the bacterium together.
Endolysins dissolve the peptidoglycan cell wall of bacteria and this results in the cell basically disintegrating by rupture through its defective cell wall and the cell therefore dying. Bacteriophages exploit this mechanism because cell rupture results in the release of virus particles from inside the infected bacterium which can then go on to infect other bacterial cells.
Certain types of bacteria, so called gram positive bacteria have more peptidoglycan than gram negative bacteria. In addition, gram negative bacteria have an outer membrane which protects its peptidoglycan layer.
This is getting confusing!
Bear with me! This outer membrane means that gram negative bacteria are essentially protected from attack by endolysins. However, gram positive bacteria are susceptible.
So these endolysin-containing creams will then kill all gram positive bacteria on the skin?
No. Endolysins are highly specific for certain types of peptidoglycans which essentially limits them to certain species of bacteria. This means that the risk of bacterial resistance developing is reduced. Also, healthy bacteria in the skin (or other organ) microflora can be left unaffected.
[Schmelcher M, Donovan, DM, Loessner MJ. Bacteriophage endolysins as novel antimicrobials. Future Microbiol 2012;7(10):1147-1171.]
Are these the new alternative to antibiotics then?
If these endolysins work in clinical practice, they would certainly be far more desirable than broad-spectrum antibiotics which kill all sensitive organisms during treatment.
Their potential use in the control of food-borne pathogens in food safety, in veterinary medicine in bovine mastitis, plant agriculture and treatment of gram positive bacterial infections in mice have all been investigated.
[Callewaert L, Walmagh M, Michiels CW et al. Food applications of bacterial cell wall hydrolases. Curr Opin Biotechnol. 2011;22(2):164-171.]
[Oldham ER, Daley MJ. Lysostaphin: use of a recombinant bactericidal enzyme as a mastitis therapeutic. J Dairy Sci. 1991;74(12):4175-82.]
[Loeffler JM, Djurkovic S, Fischetti VA. Phage lytic enzyme Cpl-1 as a novel antimicrobial for pneumococcal bacteremia. Infect Immun 2003;71(11):6199-6204.]
What about studies in humans?
These are yet to start. The company who have created an endolysin specifically targeting Staphylococcus aureus have undertaken very small observational trials, for example on seven patients with rosacea who were observed for 30 minutes. The research was then expanded to eight patients with recurring dermatitis. It is not stated as to how long they were observed but in five of the eight patients, there was a reported relief of symptoms, less corticosteroid use and a decrease in Staph aureus on the skin. However, randomized controlled clinical trials in humans are sadly lacking and it is not clear from the literature as to why this is.
[Herpers BL, Leeson N. Endolysins: redefining antibacterial therapy. Future Microbiol. 2015;10(3):309-11.]
So should we use these creams?
The main worry with the use of endolysins administered orally or intravenously is that there are potential risks such as an immune reaction to the endolysin itself or to the bacterial cell proteins that would be released after bacterial cell rupture.
It is thought that endolysins applied as creams may avoid or reduce these risks but with the absence of robust clinical trials, it is difficult to recommend them at all, especially as patients tell me that a 100ml tube of the cream is rather pricey and beyond the reach of many in the population.
Dr Sandy Flann, Consultant Dermatologist.