Abstract
Antimicrobial peptides (AMPs) are promising novel antibiotics since they have shown antimicrobial activity against a wide range of bacterial species, including multiresistant bacteria; however, toxicity is the major barrier to convert antimicrobial peptides into active drugs. A profound and proper understanding of the complex interactions between these peptides and biological membranes using biophysical tools and model membranes seems to be a key factor in the race to develop a suitable antimicrobial peptide therapy for clinical use. In the search for such therapy, different combined approaches with conventional antibiotics have been evaluated in recent years and demonstrated to improve the therapeutic potential of AMPs. Some of these approaches have revealed promising additive or synergistic activity between AMPs and chemical antibiotics. This review will give an insight into the possibilities that physicochemical tools can give in the AMPs research and also address the state of the art on the current promising combined therapies between AMPs and conventional antibiotics, which appear to be a plausible future opportunity for AMPs treatment.
Highlights
Antibiotic resistance is a considerable problem in the population regarding public health and clinical practice
Feng et al (2015) demonstrated synergistic activity between a group of short cationic antimicrobial peptides combined with traditional antibiotics against Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, and P. aeruginosa), Gram-positive (Staphylococcus epidermidis, Streptococcus pneumoniae, and Staphylococcus aureus,) Some of the peptides evaluated were from the laboratory library, some were analogs of a melittin B and cecropin A hybrid peptide, and others were derived from the N-terminus of L1, the ribosomal protein of Helicobacter pylori
Antimicrobial peptides are promising new molecules that can be de novo designed in order to meet the challenge of multiresistant bacteria but avoiding host side effects
Summary
Antibiotic resistance is a considerable problem in the population regarding public health and clinical practice. Some mechanisms of resistance to natural AMPs were described [as for example upregulation of efflux pumps, membrane and cell envelope alterations, proteolytic degradation of the peptides, biofilm formation and lipopolysaccharide (LPS) modification (Segev-Zarko et al, 2018)], with proper concentrations and in combination with antibiotics, synthetic AMPs arise as interesting new antimicrobial agents to fight multiresistant bacteria (Fox, 2013; Riool et al, 2017) To consider these molecules to be a therapeutic option and overcome clinical setbacks, a worldwide work is done with the aim to understand their mechanisms of action, promote the reduction of cellular toxicity, make them protease resistant, make them more stable and manufacture them on a large scale in a costeffective manner (Marr et al, 2006; Yount and Yeaman, 2012; Mishra et al, 2017). The future development of new kind of synergistic therapies will require a proper biophysical understanding of the peptidemembrane interactions together with the antibiotic biochemical activity
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