Human Antimicrobial Peptides: Spectrum, Mode of Action and Resistance Mechanisms
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Human Antimicrobial Peptides: Spectrum, Mode of Action and Resistance Mechanisms Bibi Sedigheh Fazly Bazzaz1,2 · Shabnam Seyedi3 · Narjes Hoseini Goki3 · Bahman Khameneh2 Accepted: 22 October 2020 © Springer Nature B.V. 2020
Abstract Overuse of antibiotics is one of the important factors that contribute to developing antimicrobial resistance. Many studies have been conducted to find out promising solutions to overcome the problems. Antimicrobial peptides (AMPs) are fundamental components of human innate immunity. They have an important role in the treatment of a wide range of diseases, including cancer, allergies, and also in warding off invading pathogens. In the case of infectious disease, the AMPs exhibit broad-spectrum activity against a wide range of pathogens including Gram-positive and -negative bacteria, yeasts, fungi, and enveloped viruses. These peptides have been isolated from various sources such as microorganisms, plants, invertebrates, and vertebrates. The peptides show distinct physicochemical and structural properties but most of them are small cationic peptides with amphipathic properties. In this review, an overview of the classification, antimicrobial activities, mode of action, and mechanism of resistance of human AMPs will be provided. These peptides are categorized into three main groups. The defensins are cationic peptides containing six cysteine residues with three intramolecular disulfide bridges. In humans, two classes of defensins could be found, α-defensins and β-defensins. The second group is cathelicidins that only one AMP, LL-37, has been found in humans. This peptide is derived from proteolytic digestion of the C-terminal of human CAP18 protein. The third group is the family of histatins that are small cationic histidine-rich peptides, and mainly present in human saliva. The last two groups have random coil conformation in hydrophilic environments and α-helices in a hydrophobic environment. Keywords Human antimicrobial peptides · Antibiotic resistance · LL-37 · Histatins · Defensins
Introduction Antibacterial resistance by multidrug-resistant (MDR) pathogens has become a global health challenge and threatens the health of societies. The emergence of resistant infections leads to existing antibacterial drugs becoming less effective or even ineffective and therefore, there is an urgent need for the development of new antibacterial agents (Khameneh et al. 2016). The death by drug-resistant bacterial infections * Bahman Khameneh [email protected] 1
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
2
Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
3
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
in each year for USA, EU, and India was 23,000, 25,000, and 58,000, respectively (Chaudhary 2016). Additionally, without developing novel approaches to combat MDR pathogens, many fields of medicine such as su
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