Construction of a genetically modified T7Select phage system to express the antimicrobial peptide 1018

Lemon, David J.; Kay, Matthew; Titus, James K; Ford, April A; Chen, Wen; Hamlin, Nicholas J; Hwang, Young Hwan

doi:10.1007/s12275-019-8686-6

Cited by 24 publications

(13 citation statements)

References 28 publications

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“…One approach is to clone a genetic expression system for a broad-spectrum AMP, i.e., promoter, AMP coding unit, transcriptional terminator, within a bacterial virus genome. The idea is that the bacterial virus encoding the AMP (or any bactericidal agent) will infect sensitive bacterial cells within the infected organism, and the lysed recipient cell will release the broad-spectrum AMP, which in turn will indiscriminately kill multiple pathogenic bacterial species within the milieu [45]. This idea is based on the expense involved in synthesizing therapeutic doses of AMP, toxicity considerations, and their relative instability, particularly in serum [46,47].…”

Section: Resultsmentioning

confidence: 99%

Bacterial Virus Lambda Gpd-Fusions to Cathelicidins, α- and β-Defensins, and Disease-Specific Epitopes Evaluated for Antimicrobial Toxicity and Ability to Support Phage Display

Hayes

2019

Viruses

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We showed that antimicrobial polypeptides, when translated as gene fusions to the bacteriophage lambda capsid decoration protein gpD, formed highly toxic molecules within E. coli, suggesting that they can retain their antimicrobial activity conformation when fused to gpD. These include gpD-fusions to human and porcine cathelicidins LL37 and PR39, β-defensins HBD3 and DEFB126-Δ (deleted for its many COOH-terminal glycosylation sites), and α-defensin HD5. Antimicrobial toxicity was only observed when the peptides were displayed from the COOH-terminal, and not the NH2-terminal end, of gpD. This suggests that COOH-terminal displayed polypeptides of gpD-fusions can more readily form an active-state conformation than when they are displayed from the NH2-terminal end of gpD. The high toxicity of the COOH-displayed gpD-defensins suggests either that the fused defensin peptides can be oxidized, forming three correct intramolecular disulfide bonds within the cytosol of bacterial cells, or that the versions without disulfide bonds are highly toxigenic. We showed the high efficiency of displaying single epitope 17 amino-acid fusions to gpD on LDP (lambda display particles), even when the gpD-fusion protein was toxic. The efficient formation of high display density LDP, displaying a single disease specific epitope (DSE), suggests the utility of LDP-DSE constructs for use as single epitope vaccines (SEV).

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Section: Resultsmentioning

confidence: 99%

Bacterial Virus Lambda Gpd-Fusions to Cathelicidins, α- and β-Defensins, and Disease-Specific Epitopes Evaluated for Antimicrobial Toxicity and Ability to Support Phage Display

Hayes

2019

Viruses

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“…In a recent study, researchers modified the genome of T7Select E. coli phage by inserting coding sequences for 1080, a short peptide with a broad-spectrum anti-biofilm effect. The modified phage was more effective in eradicating established E. coli biofilms than the unmodified phage [86]. Phages can also be designed to selectively kill antibiotic resistant bacteria.…”

Section: Genetically Modified Phagesmentioning

confidence: 99%

Phages for Biofilm Removal

2020

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Biofilms are clusters of bacteria that live in association with surfaces. Their main characteristic is that the bacteria inside the biofilms are attached to other bacterial cells and to the surface by an extracellular polymeric matrix. Biofilms are capable of adhering to a wide variety of surfaces, both biotic and abiotic, including human tissues, medical devices, and other materials. On these surfaces, biofilms represent a major threat causing infectious diseases and economic losses. In addition, current antibiotics and common disinfectants have shown limited ability to remove biofilms adequately, and phage-based treatments are proposed as promising alternatives for biofilm eradication. This review analyzes the main advantages and challenges that phages can offer for the elimination of biofilms, as well as the most important factors to be taken into account in order to design effective phage-based treatments.

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“…Thus, AMPs, with all their properties and mechanisms of action (structural, therapeutic), are incredibly suitable molecules in the treatment, especially of infections resistant to many drugs (mainly resistant to antibiotics) [ 105 , 106 , 107 , 108 ]. All future research should aim at discovering the improvement of AMPs intake and their action, and their action combined with other antimicrobial agents (antibiotics, bacteriophages) [ 109 , 110 , 111 ]. This mainly refers to their biocompatibility action in the immunomodulation system [ 84 , 101 , 107 ].…”

Section: Biofilm Treatment Strategiesmentioning

confidence: 99%

The Principles, Mechanisms, and Benefits of Unconventional Agents in the Treatment of Biofilm Infection

Talapko

Škrlec

2020

Pharmaceuticals

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Today, researchers are looking at new ways to treat severe infections caused by resistance to standard antibiotic therapy. This is quite challenging due to the complex and interdependent relationships involved: the cause of infection–the patient–antimicrobial agents. The sessile biofilm form is essential in research to reduce resistance to very severe infections (such as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter spp). The purpose of this study is to elucidate the mechanisms of the occurrence, maintenance, and suppression of biofilm infections. One form of biofilm suppression is the efficient action of natural antagonists of bacteria—bacteriophages. Bacteriophages effectively penetrate the biofilm’s causative cells. They infect those bacterial cells and either destroy them or prevent the infection spreading. In this process, bacteriophages are specific, relatively easy to apply, and harmless to the patient. Antimicrobial peptides (AMPs) support the mechanisms of bacteriophages’ action. AMPs could also attack and destroy infectious agents on their own (even on biofilm). AMPs are simple, universal peptide molecules, mainly cationic peptides. Additional AMP research could help develop even more effective treatments of biofilm (bacteriophages, antibiotics, AMPs, nanoparticles). Here, we review recent unconventional agents, such as bacteriophages and AMPs, used for eradication of biofilm, providing an overview of potentially new biofilm treatment strategies.

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Construction of a genetically modified T7Select phage system to express the antimicrobial peptide 1018

Cited by 24 publications

References 28 publications

Bacterial Virus Lambda Gpd-Fusions to Cathelicidins, α- and β-Defensins, and Disease-Specific Epitopes Evaluated for Antimicrobial Toxicity and Ability to Support Phage Display

Bacterial Virus Lambda Gpd-Fusions to Cathelicidins, α- and β-Defensins, and Disease-Specific Epitopes Evaluated for Antimicrobial Toxicity and Ability to Support Phage Display

Phages for Biofilm Removal

The Principles, Mechanisms, and Benefits of Unconventional Agents in the Treatment of Biofilm Infection

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