The value of antimicrobial peptides in the age of resistance

Magana, Maria; Muthuirulan, Pushpanathan; Santos, Ana L.E.; Leanse, Leon G.; Fernández, Michael; Ioannidis, Anastasios; Giulianotti, Marc A.; Apidianakis, Yiorgos; Bradfute, Steven B.; Ferguson, Andrew L.; Cherkasov, Artem; Seleem, Mohamed N.; Pinilla, Clemencia; Fuente-Núñez, César de la; Lazaridis, Themis; Dai, Tianhong; Houghten, Richard A.; Hancock, Robert E. W.; Tegos, George P.

doi:10.1016/s1473-3099(20)30327-3

Cited by 757 publications

(637 citation statements)

References 164 publications

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“…), have been developed to improve the targeting mechanism of AMPs. Furthermore, nanotubes, quantum dots, graphene, and metal nanoparticles have been proposed to be a potential method to enhance drug delivery of AMPs (Magana et al, 2020). Hybrid peptides have also been used to build targeting peptides.…”

Section: Current Progress and Application Of Antimicrobial Peptides Mmentioning

confidence: 99%

Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

et al. 2020

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Antimicrobial peptides (AMPs) are a class of small peptides that widely exist in nature and they are an important part of the innate immune system of different organisms. AMPs have a wide range of inhibitory effects against bacteria, fungi, parasites and viruses. The emergence of antibiotic-resistant microorganisms and the increasing of concerns about the use of antibiotics resulted in the development of AMPs, which have a good application prospect in medicine, food, animal husbandry, agriculture and aquaculture. This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. The research progress on antivirus peptides, especially anti-coronavirus (COVID-19) peptides, has been introduced given the COVID-19 pandemic worldwide in 2020.

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Section: Current Progress and Application Of Antimicrobial Peptides Mmentioning

confidence: 99%

Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

et al. 2020

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“…Nevertheless, the widespread application of AMPs is limited by a perception that peptides are expensive to produce, susceptible to proteases, and display high cytotoxicity (15)(16)(17). Peptide production costs have decreased over the past years due to advances in solid-and liquid-phase peptide synthesis (18,19), and production of recombinant peptides in Escherichia coli (20) and yeast (21). Peptides can be engineered to increase their chemical and proteolytic stability via backbone cyclization (22), side chain-to-side chain cyclization (23), or the inclusion of stereochemical amino acids (24).…”

Section: Introductionmentioning

confidence: 99%

Mode-of-Action of Antimicrobial Peptides: Membrane Disruption vs. Intracellular Mechanisms

Benfield

Henriques

2020

Front. Med. Technol.

194

139

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Antimicrobial peptides are an attractive alternative to traditional antibiotics, due to their physicochemical properties, activity toward a broad spectrum of bacteria, and mode-of-actions distinct from those used by current antibiotics. In general, antimicrobial peptides kill bacteria by either disrupting their membrane, or by entering inside bacterial cells to interact with intracellular components. Characterization of their mode-of-action is essential to improve their activity, avoid resistance in bacterial pathogens, and accelerate their use as therapeutics. Here we review experimental biophysical tools that can be employed with model membranes and bacterial cells to characterize the mode-of-action of antimicrobial peptides.

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“…Restoring the potency of antibiotics that are no longer in clinical use due to lack of efficacy or bacterial resistance is one potential route to extend the life of current therapies. Cationic antimicrobial peptides (AMPs) are found widely in nature and have been of interest as novel therapeutics [1][2][3]. AMPs are believed to act via interaction with bacterial membranes, leading to increased cell permeability or membrane disruption.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in Silico Modelling of the Potential Dual Mechanistic Activity of Small Cationic Peptides Potentiating the Antibiotic Novobiocin against Susceptible and Multi-Drug Resistant Escherichia coli

Passarini

Resende²,

Soares³

et al. 2020

IJMS

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Cationic antimicrobial peptides have attracted interest, both as antimicrobial agents and for their ability to increase cell permeability to potentiate other antibiotics. However, toxicity to mammalian cells and complexity have hindered development for clinical use. We present the design and synthesis of very short cationic peptides (3–9 residues) with potential dual bacterial membrane permeation and efflux pump inhibition functionality. Peptides were designed based upon in silico similarity to known active peptides and efflux pump inhibitors. A number of these peptides potentiate the activity of the antibiotic novobiocin against susceptible Escherichia coli and restore antibiotic activity against a multi-drug resistant E. coli strain, despite having minimal or no intrinsic antimicrobial activity. Molecular modelling studies, via docking studies and short molecular dynamics simulations, indicate two potential mechanisms of potentiating activity; increasing antibiotic cell permeation via complexation with novobiocin to enable self-promoted uptake, and binding the E. coli RND efflux pump. These peptides demonstrate potential for restoring the activity of hydrophobic drugs.

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The value of antimicrobial peptides in the age of resistance

Cited by 757 publications

References 164 publications

Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

Mode-of-Action of Antimicrobial Peptides: Membrane Disruption vs. Intracellular Mechanisms

Synthesis and in Silico Modelling of the Potential Dual Mechanistic Activity of Small Cationic Peptides Potentiating the Antibiotic Novobiocin against Susceptible and Multi-Drug Resistant Escherichia coli

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