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Antimicrobial peptides

What are they, how do they work, and why should we use them?

20 June 2018, at 3:47pm

Antimicrobial resistance is a hot topic in both human and veterinary medicine, with concerns flagged that inappropriate use of antibiotics may have contributed to an increase in bacterial resistance worldwide (Santoro and Maddox, 2014). This has largely driven the search for novel compounds to either replace or supplement conventional antibiotics and there are now numerous products on the veterinary market that utilise anti-microbial peptides (AMPs), either through the addition of synthetic AMPs or through the inclusion of compounds known to stimulate production of naturally occurring ones. 

AMPs are small, cationic polypeptides which play a fundamental role in the innate immune system. They possess broad spectrum activity against bacteria, viruses and fungi, and modify the local inflammatory response through promotion of leucocyte chemotaxis. They are secreted from epithelial and immune cells, with upregulation occurring in the face of infection or injury. The two major sub-families in mammals are defensins and cathelicidins, which exhibit similar physical and functional properties.

AMPs are small, cationic polypeptides which play a fundamental role in the innate immune system

In the face of invasion from a pathogen, AMPs are involved in many different processes such as the recruitment of other immune cells and through more direct effects on bacteria/fungi. Defensins can directly attach to the cell wall of these pathogens and, due to being positively charged, they are drawn into the negatively charged cell membrane and pair up to create a pore, ultimately causing cellular disruption and death.

The potential importance of skin defensins has been highlighted in studies of various skin disorders, for example, the comparison of lesional skin from humans with atopic dermatitis to the skin of humans with psoriasis. The former group demonstrate a significantly lower defensin expression and are more prone to skin infection, despite both conditions being associated with a defective skin barrier (Howell, 2007). It has therefore been hypothesised that a decreased production of AMPs or production of nonfunctional AMPs could be a possible cause of the higher susceptibility to skin infection in atopic dermatitis. 

However, in contrast to this, other studies have noted a significant increase in the expression of some AMPs in human and canine atopic dermatitis patients. A study by Santoro and colleagues (2013) specifically studied AMP expression in actively infected skin of canine atopic dermatitis patients and found higher expression of some AMPs and lower expression of others. They suggested it could be possible that an alteration of the ratio between AMPs is the cause of increased infections in these patients.

Harnessing this knowledge for therapeutic application is an area of increasing interest. Certain plant extracts affect levels of AMPs; a recent study in atopic dogs demonstrated a reduction in Staphylococcus spp. after 14 days of daily treatment with a water-based spray containing 0.1 percent Peumus boldus leaf and Spiraea ulmaria, compared to a control group who just received a water-based spray (Santoro et al., 2018). 

From conducted studies, it is clear that AMPs are an important component of the innate immune system to defend against external micro-organisms and clearly warrant further investigation with regards to their role in modulating skin disease and how they can be utilised further as therapeutic agents.

References
Author Year Title
Howell, M. D. 2007 Current Opinion in Allergy and Clinical Immunology, 7
Santoro, D., Bunick, D., Graves, T. K. and Segre, M. 2013 Veterinary Dermatology, 24
Santoro, D., Bohannon, M., Ahrens, K., Navarro, C., Gatto, H. and Marsella, R. 2018 Research in Veterinary Science, 118
Santoro, D. and Maddox, C. W. 2015 Veterinary Dermatology, 25

Jayne Clark, BVSc, BSc(Hons), GPCert SAM, MRCVS, worked in small animal clinical practice for 10 years before moving into industry as a technical advisor. She has an interest in all aspects of canine and feline medicine, particularly anaesthesia, analgesia and endocrinology.

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