Therapeutic Potential of Host Defense Peptides in Antibiotic-resistant Infections

Abstract

The emergence of infections caused by multi-drug resistant (MDR) pathogens pose a major burden to modern healthcare. Exacerbating this issue is the substantial decline in development of new classes of antibiotics by pharmaceutical companies. This has led to renewed interest in the therapeutic potential of natural anti-infective agents such as host defense peptides (HDPs). The broad antimicrobial and immunomodulatory activities of HDPs and their synthetic derivatives, coupled with the fact that they do not readily induce microbial resistance, makes them extremely valuable leads in the development of new treatment strategies for MDR infections. This review examines our knowledge of the mechanisms behind multi-drug resistance as well as the properties of HDPs and their therapeutic potential, especially in the case of MDR infections. Challenges to their development as new therapeutics are also discussed.

The Zeamine Antibiotics Affect the Integrity of Bacterial Membranes

“…CAMPs are a large group of bioactive peptides produced by virtually all species of life as a major part of their primary defense system (25,26). In addition to their broad spectrum of activity against bacteria, fungi, parasites, viruses, and even cancer cells, they display a variety of immunomodulatory effects (27).…”

“…The CAMPs then bind to the anionic lipid head groups of the cytoplasmic membrane and insert themselves into the outer leaflet, parallel to the plane of the bilayer, leading to the displacement of lipids. Through hydrophobic interactions, they subsequently insert themselves into the membrane interior (25). Similar to the zeamines, CAMPs exhibit a strong preference for negatively charged bacterial over zwitterionic eukaryotic membranes.…”

The intrinsic antimicrobial activity of citric acid-coated manganese ferrite nanoparticles is enhanced after conjugation with the antifungal peptide Cm-p5

“…Their use as anti-infective tools represents a novel approach for the development of antimicrobial therapies. 4,5 Even though such peptides have been shown to be both broad spectrum (having antimicrobial, anticancer, immunomodulatory, wound healing and angiogenesis properties) and significantly potent in preclinical studies, this success has not been transmitted to clinical practice yet. 6 The major disadvantages of AMPs have been low stability, cytotoxicity, biodistribution, and high production costs.…”

“…6 The major disadvantages of AMPs have been low stability, cytotoxicity, biodistribution, and high production costs. 4,7 Dovepress Dovepress 3850 lopez-abarrategui et al Development of nanoparticles for delivery or conjugation of AMPs could represent an alternative to bypass the abovementioned clinical obstacles. 8 In fact, the antimicrobial activity of different types of nanoparticles has been demonstrated.…”

Development of a novel antimicrobial peptide AWRK6

“…These two factors, therefore, become the driving force in the search for novel drugs against pathogenic bacteria (Shlaes and Spellberg, 2012). There is an urgent need to find new types of antibiotics to maintain our existing capability to treat infectious diseases, especially those caused by multidrug-resistant (MDR) organisms (Afacan et al, 2012). Antimicrobial peptides (AMPs) are important and highly conserved components of innate immune responses in most multicellular organisms.…”