Protein-Based Systems for Topical Antibacterial Therapy

Thapa, Raj Kumar; Grønlien, Krister Gjestvang; Tønnesen, Hanne

doi:10.3389/fmedt.2021.685686

Cited by 4 publications

(4 citation statements)

References 177 publications

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“…The wound dressings performed multiple functions: stimulating skin cell migration, proliferation, and paracrine effects; promoting endothelial morphogenesis and angiogenesis; and reducing tissue inflammation and oxidative stress under TGFβ1 and high glucose conditions. These wound dressings more quickly accelerated wound closure than using growth factors 120,121 , protein 122 , exogenous cells 123 , or oxygen therapy in the same animal model 73 . A limitation of the current study is that the rodent models do not fully mimic the complex human pathophysiology, and implications of microvascular occlusive disease that may occur in the setting of chronic diabetes.…”

Section: Discussionmentioning

confidence: 99%

Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing

Guan

Zhong

et al. 2023

npj Regen Med

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Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFβ receptor II inhibitor (PTβR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTβR2I inhibits the TGFβ1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTβR2I does not interfere with the TGFβ1/Smad2/3 pathway that is required to regulate myofibroblasts, a critical cell type for wound healing. The hydrogel’s ability to scavenge ROS in diabetic wounds further decreases inflammation. Single-dose application of the wound dressing significantly accelerates wound healing with complete wound closure after 14 days. Overall, using wound dressings capable of adaptively modulating TGFβ pathways provides a new strategy for diabetic wound treatment.

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Section: Discussionmentioning

confidence: 99%

Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing

Guan

Zhong

et al. 2023

npj Regen Med

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“…When formulated with PaP1, the increased in vivo potency of mupirocin and gentamicin, two antibiotics currently used for topical antibacterial treatment ( Lipsky and Hoey, 2009 ; Thapa et al, 2021 ), could be the result of the peptide permeabilizing the bacterial membrane. This would stimulate the rapid intracellular accumulation of the antibiotic and easier access to their cytosolic targets (isoleucyl-tRNA synthetase for mupirocin, 30S ribosomal subunit for gentamicin).…”

Section: Discussionmentioning

confidence: 99%

PaP1, a Broad-Spectrum Lysin-Derived Cationic Peptide to Treat Polymicrobial Skin Infections

2022

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Most skin infections, including those complicating burns, are polymicrobial involving multiple causative bacteria. Add to this the fact that many of these organisms may be antibiotic-resistant, and a simple skin lesion or burn could soon become life-threatening. Membrane-acting cationic peptides from Gram-negative bacteriophage lysins can potentially aid in addressing the urgent need for alternative therapeutics. Such peptides natively constitute an amphipathic region within the structural composition of these lysins and function to permit outer membrane permeabilization in Gram-negative bacteria when added externally. This consequently allows the lysin to access and degrade the peptidoglycan substrate, resulting in rapid hypotonic lysis and bacterial death. When separated from the lysin, some of these cationic peptides kill sensitive bacteria more effectively than the native molecule via both outer and cytoplasmic membrane disruption. In this study, we evaluated the antibacterial properties of a modified cationic peptide from the broad-acting lysin PlyPa01. The peptide, termed PaP1, exhibited potent in vitro bactericidal activity toward numerous high priority Gram-positive and Gram-negative pathogens, including all the antibiotic-resistant ESKAPE pathogens. Both planktonic and biofilm-state bacteria were sensitive to the peptide, and results from time-kill assays revealed PaP1 kills bacteria on contact. The peptide was bactericidal over a wide temperature and pH range and could withstand autoclaving without loss of activity. However, high salt concentrations and complex matrices were found to be largely inhibitory, limiting its use to topical applications. Importantly, unlike other membrane-acting antimicrobials, PaP1 lacked cytotoxicity toward human cells. Results from a murine burn wound infection model using methicillin-resistant Staphylococcus aureus or multidrug-resistant Pseudomonas aeruginosa validated the in vivo antibacterial efficacy of PaP1. In these studies, the peptide enhanced the potency of topical antibiotics used clinically for treating chronic wound infections. Despite the necessity for additional preclinical drug development, the collective data from our study support PaP1 as a potential broad-spectrum monotherapy or adjunctive therapy for the topical treatment of polymicrobial infections and provide a foundation for engineering future lysin-derived peptides with improved antibacterial properties.

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“…Zein, a plant protein found in maize endosperm composed of four nonpolar amino acids (glutamine, leucine, proline, and alanine), was suggested as potent topical antibacterial formulations. However, no commercial products of zein for the topical antibacterial therapy of infected wounds were reported [ 64 ]. Therefore, considering the above-mentioned recent publications, proteins could be considered promising strategies for the development of formulations to treat wounds, including the infected ones.…”

Section: Treatments For Topical Infected Woundsmentioning

confidence: 99%

The Use of Proteins, Lipids, and Carbohydrates in the Management of Wounds

et al. 2023

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Despite the fact that skin has a stronger potential to regenerate than other tissues, wounds have become a serious healthcare issue. Much effort has been focused on developing efficient therapeutical approaches, especially biological ones. This paper presents a comprehensive review on the wound healing process, the classification of wounds, and the particular characteristics of each phase of the repair process. We also highlight characteristics of the normal process and those involved in impaired wound healing, specifically in the case of infected wounds. The treatments discussed here include proteins, lipids, and carbohydrates. Proteins are important actors mediating interactions between cells and between them and the extracellular matrix, which are essential interactions for the healing process. Different strategies involving biopolymers, blends, nanotools, and immobilizing systems have been studied against infected wounds. Lipids of animal, mineral, and mainly vegetable origin have been used in the development of topical biocompatible formulations, since their healing, antimicrobial, and anti-inflammatory properties are interesting for wound healing. Vegetable oils, polymeric films, lipid nanoparticles, and lipid-based drug delivery systems have been reported as promising approaches in managing skin wounds. Carbohydrate-based formulations as blends, hydrogels, and nanocomposites, have also been reported as promising healing, antimicrobial, and modulatory agents for wound management.

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Protein-Based Systems for Topical Antibacterial Therapy

Cited by 4 publications

References 177 publications

Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing

Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing

PaP1, a Broad-Spectrum Lysin-Derived Cationic Peptide to Treat Polymicrobial Skin Infections

The Use of Proteins, Lipids, and Carbohydrates in the Management of Wounds

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