The Influence of Polyanions and Polycations on Bacteriophage Activity

Musin, Egor V.; Kim, Aleksandr L.; Дубровский, А. В.; Kudryashova, E. B.; Ariskina, Elena V.; Tikhonenko, Sergey A.

doi:10.3390/polym13060914

Cited by 5 publications

(7 citation statements)

References 16 publications

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“…As a result, after the addition of capsules to the nutrient medium with the subsequent destruction of the PMC shell, it was shown that there was no bacteriophage activity. This effect may be related to the destruction of the shell by a proteinase with the subsequent release of monomers and dimers of the polyarginine shell, which may be the cause of bacteriophage inactivation [ 56 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

The Pathways to Create Containers for Bacteriophage Delivery

et al. 2022

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Antimicrobial resistance is a global public health threat. One of the possible ways to solve this problem is phage therapy, but the instability of bacteriophages hinders the development of this approach. A bacteriophage delivery system that stabilizes the phage is one of the possible solutions to this problem. This study is dedicated to exploring methods to create encapsulated forms of bacteriophages for delivery. We studied the effect of proteolytic enzymes on the destruction of the polyelectrolyte microcapsule shell and revealed that protease from Streptomyces griseus was able to destroy the membrane of the microcapsule (dextran sulfate/polyarginine)3 ((DS/PArg)3). In addition, the protease decreased the activity of the bacteriophage in the second hour of incubation, and the phage lost activity after 16 h. It was found that a medium with pH 9.02 did not affect the survival of the bacteriophage or E. coli. The bacteriophages were encapsulated into polyelectrolyte microcapsules (DS/PArg)3. It was established that it is impossible to use microcapsules as a means of delivering bacteriophages since the bacteriophages are inactivated. When bacteriophages were included inside a CaCO3 core, it was demonstrated that the phage retained activity before and after the dissolution of the CaCO3 particle. From the results of this study, we recommend using CaCO3 microparticles as a container for bacteriophage delivery through the acidic stomach barrier.

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Section: Resultsmentioning

confidence: 99%

The Pathways to Create Containers for Bacteriophage Delivery

et al. 2022

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“…Unfortunately, polycations exhibit significant cytotoxicity, and thus they can be harmful to living organisms. 8,9 Therefore, more and more attention is paid to understanding the potential environmental impacts of polycationic nanomaterials.…”

Section: Introductionmentioning

confidence: 99%

Effect of polycation nanostructures on cell membrane permeability and toxicity

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Lasota

et al. 2022

Environ. Sci.: Nano

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“…To the best of our knowledge, the only report of antiphage polymer is dextran, dextran sulfate, and polystyrene sulfate, which show some limited inhibition but have been neither widely explored nor compared to other polymers, and their mode of action is not studied. 37 Here we report the novel discovery that poly(acrylic acid) (PAA) is a potent inhibitor of bacteriophage infection. A library of polymers was screened, showing this material to be uniquely active, even compared to other poly(carboxylic acid)s. The polymer prevents infection and is shown to not interfere with recombinant protein expression procedures in bacteria.…”

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confidence: 99%

“…It has recently been demonstrated that sulfated polymers, which mimic heparin sulfate anchors on cell membranes, are broad-spectrum virucides against a range of human pathogenic viruses. , Poly(carboxylic acid)s have been reported to inhibit human viruses. , It is also well-established that polymers can be deployed as antibacterial agents, mimicking cationic host-defense peptides. − A polymeric/biomaterials approach to address phage contamination may offer a scalable and practical solution. To the best of our knowledge, the only report of antiphage polymer is dextran, dextran sulfate, and polystyrene sulfate, which show some limited inhibition but have been neither widely explored nor compared to other polymers, and their mode of action is not studied …”

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“…Many mammalian viruses (but not known for phages) engage cell surface heparin sulfate, and polymeric sulfates have been found to be virucidal. ,, PMA and PAA have been reported to inhibit human cell infection by mammalian viruses but have not been explored for bacteriophage inhibition . Dextran sulfate may partially inhibit phage infection, but the mechanism has not been explored. Here, poly(styrenesulfonate) was found to have no phage-inhibiting activity (Figure S18) in our assays, in contrast to mammalian viruses where polysulfonates are virucidal .…”

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Anionic Synthetic Polymers Prevent Bacteriophage Infection

et al. 2023

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Bioprocessing and biotechnology exploit microorganisms (such as bacteria) for the production of chemicals, biologics, therapies, and food. A major unmet challenge is that bacteriophage (phage) contamination compromises products and necessitates shut-downs and extensive decontamination using nonspecific disinfectants. Here we demonstrate that poly(acrylic acid) prevents phage-induced killing of bacterial hosts, prevents phage replication, and that induction of recombinant protein expression is not affected by the presence of the polymer. Poly(acrylic acid) was more active than poly(methacrylic acid), and poly(styrenesulfonate) had no activity showing the importance of the carboxylic acids. Initial evidence supported a virustatic, not virucidal, mechanism of action. This simple, low-cost, mass-produced additive offers a practical, scalable, and easy to implement solution to reduce phage contamination.I t is now possible to edit biosynthetic pathways in bacteria to produce high-value chemicals and natural products. 1 Bacteria are widely used in food production. For bacteria to be used in any application area, it is essential to exclude bacteriophage (phage−bacteria selective viruses), which are a common cause of infection that leads to financial and scientific losses. Bacteriophages are among the most abundant organisms on earth and are present wherever their hosts are. 2 Phages have potential as alternatives to antibiotics 3−5 for food safety 6 and veterinary settings. 7 Phages are also widely used in biotechnology for ligand selection 8−10 and other areas. 8,11 Despite their wide biotechnological use, phage contamination in bacterial cultures leads to a complete loss of the culture. This has significant cost implications for both academic and industrial laboratories that have invested in isolating and preparing these bacterial cultures. For example, in the food industry, it is not possible to remove all phage from raw materials, and this can lead to process collapse. 12−14 Currently, good microbiology practice, aseptic conditions, and vigorous cleaning or autoclaving are the primary mitigation tools. These methods are not always successful, as phages are robust and can survive in almost every condition. 15 One option is to engineer bacterial strains, which are intrinsically resistant to phage, using, for example, gene editing technology, but this is not trivial and might not be suitable for all hosts. 16 Changing processes or re-engineering strains that have been optimized for a particular biorefinery challenge is not simple: a pragmatic solution would be an antiphage additive, in much the same way that antibiotics are routinely used in mammalian cell culture, to prevent bacterial infection. 17 There are many studies on the use of phage in treatment 7,18,19 and for ligand screening, 9,10,20 but very few on tools to inhibit them. In contrast, mammalian viruses have been investigated for the discovery of viral inhibitors 21,22 and for repurposing of existing inhibitors. 23

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The Influence of Polyanions and Polycations on Bacteriophage Activity

Cited by 5 publications

References 16 publications

The Pathways to Create Containers for Bacteriophage Delivery

The Pathways to Create Containers for Bacteriophage Delivery

Effect of polycation nanostructures on cell membrane permeability and toxicity

Anionic Synthetic Polymers Prevent Bacteriophage Infection

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