Abstract
Alarming data about increasing resistance to conventional antibiotics are reported, while at the same time the development of new antibiotics is stagnating. Skin and soft tissue infections (SSTIs) are mainly caused by the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) which belong to the most recalcitrant bacteria and are resistant to almost all common antibiotics. S. aureus and P. aeruginosa are the most frequent pathogens isolated from chronic wounds and increasing resistance to topical antibiotics has become a major issue. Therefore, new treatment options are urgently needed. In recent years, research focused on the development of synthetic antimicrobial peptides (AMPs) with lower toxicity and improved activity compared to their endogenous counterparts. AMPs appear to be promising therapeutic options for the treatment of SSTIs and wounds as they show a broad spectrum of antimicrobial activity, low resistance rates and display pivotal immunomodulatory as well as wound healing promoting activities such as induction of cell migration and proliferation and angiogenesis. In this review, we evaluate the potential of AMPs for the treatment of bacterial SSTIs and wounds and provide an overview of the mechanisms of actions of AMPs that contribute to combat skin infections and to improve wound healing. Bacteria growing in biofilms are more resistant to conventional antibiotics than their planktonic counterparts due to limited biofilm penetration and distinct metabolic and physiological functions, and often result in chronification of infections and wounds. Thus, we further discuss the feasibility of AMPs as anti-biofilm agents. Finally, we highlight perspectives for future therapies and which issues remain to bring AMPs successfully to the market.
Highlights
Antimicrobial peptides (AMPs) are increasingly coming into the focus as new treatment strategies for bacterial infections
As skin and soft tissue infections (SSTIs) are mainly caused by S. aureus, with methicillin-resistant Staphylococcus aureus (MRSA) accounting for 50% of all SSTIs, and Gram-negative pathogens such as P. aeruginosa and vancomycin-resistant Enterococcus (VRE) are increasingly isolated, especially from chronic wounds, the current resistance situation constitutes a major issue for the treatment of these infections (Guillamet and Kollef, 2016)
Compared to planktonic cells, bacteria growing in biofilms are 10- to 1,000-fold more resistant to conventional antibiotics, mostly due to limited penetration of antibiotics, and are estimated to account for at least 65% of all human infections and often result in chronification of infections and wounds
Summary
Antimicrobial peptides (AMPs) are increasingly coming into the focus as new treatment strategies for bacterial infections. The golden era of antibiotic discovery that started almost one century ago when Fleming discovered penicillin in 1928 and that can be accounted as one of the greatest achievements of modern medicine seems to be over. AMPs for Treatment of Skin Infections and Wounds up to the 1980s it was popular opinion that infections have been conquered (Spellberg et al, 2004, 2008), today alarming data about increasing resistance to conventional antibiotics are reported occurring due to excessive use and misuse in medicine, food industry, and agriculture. The current resistance situation raises concerns about a post-antibiotic era with no antimicrobial treatment options. Estimates claim that by 2050 worldwide 10 million people a year will die from infections caused by drug-resistant bacteria (Cordes et al, 2014) and the World Health Organization classifies the appearance of antibiotic resistance as one of the biggest threats to human health.
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