Abstract
Antimicrobial peptides (AMPs) or host defense peptides protect the host against various pathogens such as yeast, fungi, viruses and bacteria. AMPs also display immunomodulatory properties ranging from the modulation of inflammatory responses to the promotion of wound healing. More interestingly, AMPs cause cell disruption through non-specific interactions with the membrane surface of pathogens. This is most likely responsible for the low or limited emergence of bacterial resistance against many AMPs. Despite the increasing number of antibiotic-resistant bacteria and the potency of novel AMPs to combat such pathogens, only a few AMPs are in clinical use. Therefore, the current review describes (i) the potential of AMPs as alternatives to antibiotics, (ii) the challenges toward clinical implementation of AMPs and (iii) strategies to improve the success rate of AMPs in clinical trials, emphasizing the lessons we could learn from these trials.
Highlights
Antibiotic resistance is a global concern in health care as resistance mechanisms are emerging and spreading globally
They show that Antimicrobial peptides (AMPs) may induce resistance mechanisms in MRSA via this system, which involves the D-alanylation of teichoic acids, the incorporation of lysophosphatidylglycerol in the bacterial membrane, the increase of lysine biosynthesis and AMP transport systems (Arcilla et al, 2016)
(i) their broad spectrum of activity, (ii) multi-hit, non-specific and rapid mode of action, which results in limited emergence of resistance, (iii) the potential immunomodulatory properties and (iv) synergistic interactions with conventional antibiotics could eliminate the threat of multi-drug resistant (MDR) bacteria
Summary
Antibiotic resistance is a global concern in health care as (new) resistance mechanisms are emerging and spreading globally. Resistant bacterial strains have been identified for various antibiotics in clinical use. Shortly after the emergence of penicillin-resistant Staphylococcus aureus in 1940 (Abraham and Chain, 1940), several pathogenic bacteria became resistant to penicillin and to semi-synthetic penicillin, cephalosporins and newer carbapenems (Kumarasamy et al, 2010). The decline in the approval of new antibiotics by regulatory bodies has further exacerbated this problem. AMPs have been at the forefront of international efforts because they are less likely to induce bacterial resistance (Wimley and Hristova, 2011).
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