I came across this study “IL-1 beta-induced protection of keratinocytes against Staphylococcus aureus-secreted proteases is mediated by human beta defensin 21” where the researchers studied how the skin protected itself against staphylococcus aureus (“staph bacteria”). This research is important because staph bacteria is known to colonize atopic dermatitis skin, and in doing so, have resulted in worsened control of atopic dermatitis. (Note to readers: Due to many types of eczema, it is recommended to use atopic dermatitis to avoid confusion with other types of eczema like contact dermatitis).
I’m privileged to interview the lead researcher for the study, Dr Donald J Davidson MBChB PhD. Dr Davidson is the MRC Senior Research Fellow and University of Edinburgh Senior Lecturer. The Davidson Group within the MRC Centre for Inflammation Research focuses on understanding the physiological importance of cationic host defence peptides (CHDP) to host defences against bacterial and viral infections. Dr Davidson is a medical graduate of the University of Edinburgh who chose to pursue a scientific research career. He completed a PhD at the MRC Human Genetics Unit, studying the pathogenesis of cystic fibrosis lung disease, then was awarded a Wellcome Trust Travelling Research Fellowship to undertake post-doctoral training in innate immunity research at the University of British Columbia, Vancouver. You can read more of his research interests here.
MarcieMom: Thank you Dr Davidson for taking the time to help with the questions. The questions will be based on the study, but more focused on its practical implications.
Staphylococcus aureus is a resilient bacteria found on the skin that can survive in dry condition and on dry skin with little oxygen. It tends to involve areas that are warm and moist especially such as skin near mucous membranes such as the nose, mouth, genitals and anal area. It is found in less than 30% of healthy adults and generally does not cause an infection in those with healthy skin. However, as pointed out in the study, 75% to 100% of atopic dermatitis patients have staph bacteria on their lesional skin and 30% to 100% of atopic dermatitis patients have staph bacteria on their non-lesional skin (Breuer et al., 2002; Gong et al., 2006; Park et al., 2013). The problem with staph bacteria is that it secretes toxins and proteases that can worsen atopic dermatitis.
MarcieMom: From your study, protease V8 was of interest which showed it led to skin barrier dysfunction. Can you explain what you learnt about staphylococcus aureus’ interaction with atopic dermatitis skin/ normal skin and how does it damage skin integrity?
Dr Davidson: In our study we did not use the whole live bacteria, but concentrated instead on its harmful proteases. Using skin cells grown in the laboratory and collecting the substances made by the bacteria Staphylococcus aureus, we were able to show that the bacterial protease V8 was the most powerful product when it came to breaking down and damaging the skin barrier. Together with studies from other research groups, this suggested that one of the main ways these bacteria can damage skin is by producing V8, and that finding ways to block this damage may help to maintain and/or restore the skin integrity in atopic dermatitis.
Natural Skin Defence
In your study, it was mentioned that human beta defensin 2 (hBD2) is a substance on our skin that have antimicrobial properties and able to protect against skin integrity damage caused by staph bacteria protease V8. It was further noted that the level of hBD2 on atopic dermatitis skin was significantly lower than normal skin, therefore atopic dermatitis skin may be more prone to infection and unable to defend itself against staph bacteria.
MarcieMom: I hope I have understood hBD2’s role correctly; can you explain more about what you have found out about hBD2, for instance, how important is its role in maintaining skin integrity, fighting infection and the effects of protease V8?
Dr Davidson: Our bodies can make quite a wide range of substances we call antimicrobial host defence peptides (HDP). The skin is one site that produces these. These HDP have a lot of different roles in protecting us from infection and disease. hBD2 is an HDP from the defensin family. hBD2 was already known to be capable of killing bacteria in the laboratory. It is less clear if it definitely does this in normal functioning on our skin. However, it has been suggested by other researchers that the failure of atopic dermatitis skin to make as much hBD2 as one would expect (for the amount of skin inflammation or damage), could be one reason that atopic dermatitis skin lesions are prone to infection. What our new MRC-funded research discovered was that hBD2 can also stop V8 from damaging laboratory-grown skin. This worked both when we instructed the skin to make extra hBD2 (using genetic modification) and when we added hBD2 in the style of a treatment. Just how important this is in a living human remains to be seen, but it has obvious potential and shows that hBD2 can protect the skin barrier as well as kill bacteria.
MarcieMom: The interesting part of your study was its demonstration that application of hBD2 was found to be protective, and therefore a possible future eczema therapeutic. How does the application of hBD2 work? What are its protective effects?
Dr Davidson: At this point we don’t know how hBD2 protects this skin barrier integrity and we are currently applying for more funding so that we can start to work this out. It may act directly on the V8 to block the damaging effects of this bacterial protease, but we’ve found that it can also help to speed up repair where damage has occurred. So hBD2 may work in more than one way.
Is this something you foresee that can be easily added into a moisturizer or would it be more likely to be a non-steroidal topical prescription?
Dr Davidson: At this stage we are still in the discovery science phase of the research, so it is too early to predict how, and even whether, it will turn out to be a useful treatment. However, in the best case scenario for the outcome of our research, I would envisage adding hBD2 (or drugs made to mimic some of its functions) into prescription moisturizer-type creams or ointments.
How would the application of hBD2 be compared with the existing eczema measures such as bleach bath to kill staph bacteria?
Dr Davidson: I’m afraid it is too early to be able to make comparisons of that kind, until we have a better understanding of exactly how hBD2 functions to protect the skin barrier.
MarcieMom: Thank you Dr Davidson once again for your time and will certainly look forward to further breakthroughs and more studies done in this area.
Wang B, McHugh BJ, Qureshi A, Campopiano DJ, Clarke DJ, Fitzgerald JR, Dorin JR, Weller R, Davidson DJ, IL-1beta-induced protection of keratinocytes against Staphylococcus aureus-secreted proteases is mediated by human beta defensin 2, The Journal of Investigative Dermatology (2016), doi: 10.1016/j.jid.2016.08.025.
Breuer K, S HA, Kapp A, Werfel T (2002) Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol 147:55-61.
Gong JQ, Lin L, Lin T, Hao F, Zeng FQ, Bi ZG, et al. (2006) Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial. Br J Dermatol 155:680-7.
Park HY, Kim CR, Huh IS, Jung MY, Seo EY, Park JH, et al. (2013) Staphylococcus aureus Colonization in Acute and Chronic Skin Lesions of Patients with Atopic Dermatitis. Ann Dermatol 25:410-6.