Advances of peptides for antibacterial applications

Yan, Yuhan; Li, Yuanze; Zhang, Zhiwen; Wang, Xinhao; Niu, Yuzhong; Zhang, Shaohua; Xu, Wenlong; Ren, Chunguang

doi:10.1016/j.colsurfb.2021.111682

Cited by 154 publications

(88 citation statements)

References 281 publications

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“…These peptides show a broad spectrum of activity against Gram-positive and Gram-negative bacteria, fungi, viruses, and parasites ( Hancock and Diamond, 2000 ). AMP have increasingly been explored as an alternative to conventional antibiotics ( Yan et al, 2021 ). Currently, the sequences of approximately 3,200 AMP are known ( Wang et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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Stapled Anoplin as an Antibacterial Agent

et al. 2021

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Anoplin is a linear 10-amino acid amphipathic peptide (Gly-Leu-Leu-Lys-Arg-Ile-Lys-Thr-Leu-Leu-NH2) derived from the venom sac of the solitary wasp. It has broad antimicrobial activity, including an antibacterial one. However, the inhibition of bacterial growth requires several dozen micromolar concentrations of this peptide. Anoplin is positively charged and directly interacts with anionic biological membranes forming an α-helix that disrupts the lipid bilayer. To improve the bactericidal properties of anoplin by stabilizing its helical structure, we designed and synthesized its analogs with hydrocarbon staples. The staple was introduced at two locations resulting in different charges and amphipathicity of the analogs. Circular dichroism studies showed that all modified anoplins adopted an α-helical conformation, both in the buffer and in the presence of membrane mimics. As the helicity of the stapled anoplins increased, their stability in trypsin solution improved. Using the propidium iodide uptake assay in Escherichia coli and Staphylococcus aureus, we confirmed the bacterial membrane disruption by the stapled anoplins. Next, we tested the antimicrobial activity of peptides on a range of Gram-negative and Gram-positive bacteria. Finally, we evaluated peptide hemolytic activity on sheep erythrocytes and cytotoxicity on human embryonic kidney 293 cells. All analogs showed higher antimicrobial activity than unmodified anoplin. Depending on the position of the staple, the peptides were more effective either against Gram-negative or Gram-positive bacteria. Anoplin[5-9], with a lower positive charge and increased hydrophobicity, had higher activity against Gram-positive bacteria but also showed hemolytic and destructive effects on eukaryotic cells. Contrary, anoplin[2-6] with a similar charge and amphipathicity as natural anoplin effectively killed Gram-negative bacteria, also pathogenic drug-resistant strains, without being hemolytic and toxic to eukaryotic cells. Our results showed that anoplin charge, amphipathicity, and location of hydrophobic residues affect the peptide destructive activity on the cell wall, and thus, its antibacterial activity. This means that by manipulating the charge and position of the staple in the sequence, one can manipulate the antimicrobial activity.

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Section: Introductionmentioning

confidence: 99%

“…The main disadvantages of AMP are toxicity, possible immunogenicity, and protease sensitivity ( Lei et al, 2019 ; Huan et al, 2020 ). Hence, new chemical modifications of peptides should be developed to create protease-resistant, less toxic, and more antibacterially active peptides ( Yan et al, 2021 ; Li et al, 2021b ).…”

Section: Introductionmentioning

confidence: 99%

Stapled Anoplin as an Antibacterial Agent

et al. 2021

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“…The innate ability of MSC derived exosomes to deliver their cargo to the damaged tissue forms the basis of their innovative application as a drug delivery system in infection therapy. Pathogenic bacterium damage could indeed be targeted by natural delivering nanomaterials [51], for instance by the combination of mammalian microvesicles and exosomes coupled with selected natural AMPs or synthetically optimized peptidomimetics [54,196,197], in substitution for or synergy with classical antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

Marrazzo

Pizzuti

Zia³

et al. 2021

Antibiotics

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Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advantageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms.

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“…For example, barrel-stave model, toroidal-pore model, carpet model and aggregate model are the most studied and widely accepted ones. 49,50 Although having minor differences, these models all share the same key point: membrane disruption.…”

Section: Gl13k Release Studymentioning

confidence: 99%