The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases

Abstract

Abstract:Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs) are caused by a variety of pathogens and are particularly wide-spread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated.

A New Synthetic Peptide Having Two Target of Antibacterial Action in E. coli ML35

“…However, lysis percentages were very low, thereby agreeing with that reported for various AMPs; SA-2-SA-5 has 10% maximum hemolysis at 500 μg/mL and magainin 1 has maximum 3% hemolysis at 50 μM. Other natural AMPs, such as melittin, have 100% hemolytic activity at 12 μg/mL (Maher and McClean, 2006; Joshi et al, 2010; Lewies et al, 2015). Such low hemolytic capability could be associated with a lower percentage of PE in RBC external monolayer (Daleke, 2008) since it was observed that peptide 35409 preferentially interacted with this phospholipid ( Figure 5B ).…”

“…Most of them share common characteristics, such as length (12-100 residues), positive net charge and amphipathic structures; however; they have little sequence homology and a broad range of secondary structures (Lewies et al, 2015). AMPs’ most important mechanism of action lies in altering membrane organization and depolarization through electrostatic and hydrophobic interactions with negatively charged lipids on cell membrane (Yeaman and Yount, 2003; Reddy et al, 2004; Teixeira et al, 2012).…”

“…AMPs’ most important mechanism of action lies in altering membrane organization and depolarization through electrostatic and hydrophobic interactions with negatively charged lipids on cell membrane (Yeaman and Yount, 2003; Reddy et al, 2004; Teixeira et al, 2012). It has been described that AMPs can exercise their activity through peptide-membrane interactions, cell entry and binding to intracellular molecules, and inhibiting the synthesis of enzymes from cell wall, DNA, RNA, or proteins (Peters et al, 2010; Lewies et al, 2015). Additionally, AMP activity and mechanism of action have been related to their amino acid sequence, concentration, net charge, secondary structure, hydrophobicity, as well as the bacterial membrane composition (Dathe et al, 1997; Epand et al, 2005; Spindler et al, 2011).…”

Antimicrobial and Antibiofilm Peptides

“…α-helical AMPs are linear in aqueous solution and will assume amphipathic helical structures when they interact with bacterial membranes or in the presence of organic solvents [6]. Magainin-2 and LL-37 are examples of peptides that belong to this group (Figure 2a,b) [20,21]. In the α-helix conformation, the distance between two close amino acids is around 0.15 nm while the angle between them with regard to the center is around 100 degrees from the top view [18].…”

Recent insights into structure-function relationships of antimicrobial peptides

“…α‐helical AMPs have a linear structure in aqueous solution and become amphipathic helical structure upon contacting bacterial membrane or organic solvents (Mahlapuu, Hakansson, Ringstad, & Bjorn, ). Most members of this class are free of cysteine residues and contain around 50% hydrophobic residues that promote the amphiphilic conformation upon contact with a membrane (Lewies, Wentzel, Jacobs, & Du Plessis, ). Furthermore, α‐helical AMPs are often broad spectrum and are capable of interacting with various types of membranes.…”