Bacteriophages as Therapeutic Preparations: What Restricts Their Application in Medicine

Vlassov, Valentin V.; Tikunova, Nina; Morozova, Vera

doi:10.1134/s0006297920110061

Cited by 15 publications

(8 citation statements)

References 94 publications

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“…Bacteriophages are once again considered as perspective biocontrol agents for many applications, [ 38 , 39 , 40 , 41 ] including phage therapy (PT) that may provide at least an interim solution for the alleviation of the global crisis caused by the spread of multidrug-resistant bacterial pathogens [ 39 , 42 , 43 , 44 , 45 ]. Broad host range bacteriophages are highly demanded for PT.…”

Section: Discussionmentioning

confidence: 99%

RB49-like Bacteriophages Recognize O Antigens as One of the Alternative Primary Receptors

Efimov¹,

Golomidova²,

Kulikov

et al. 2022

IJMS

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The power of most of the enterobacterial O antigen types to provide robust protection against direct recognition of the cell surface by bacteriophage receptor-recognition proteins (RBP) has been recently recognized. The bacteriophages infecting O antigen producing strains of E. coli employ various strategies to tackle this nonspecific protection. T-even related phages, including RB49-like viruses, often have wide host ranges, being considered good candidates for use in phage therapy. However, the mechanisms by which these phages overcome the O antigen barrier remain unknown. We demonstrate here that RB49 and related phages Cognac49 and Whisky49 directly use certain types of O antigen as their primary receptors recognized by the virus long tail fibers (LTF) RBP gp38, so the O antigen becomes an attractant instead of an obstacle. Simultaneously to recognize multiple O antigen types, LTFs of each of these phages can bind to additional receptors, such as OmpA protein, enabling them to infect some rough strains of E. coli. We speculate that the mechanical force of the deployment of the short tail fibers (STF) triggered by the LTF binding to the O antigen or underneath of it, allows the receptor binding domains of STF to break through the O polysaccharide layer.

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Section: Discussionmentioning

confidence: 99%

RB49-like Bacteriophages Recognize O Antigens as One of the Alternative Primary Receptors

Efimov¹,

Golomidova²,

Kulikov

et al. 2022

IJMS

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“…Thus, tumor-targeting phages are promising molecules for the development of theranostics or imaging agents based on them. For the further use of bacteriophages, it is necessary to conduct full-fledged clinical trials in order to clarify issues related to dosage, methods of administration, and the possible therapeutic use of bacteriophage products [40].…”

Section: Discussionmentioning

confidence: 99%

Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications

et al. 2021

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Background: Tumor-targeting bacteriophages can be used as a versatile new platform for the delivery of diagnostic imaging agents and therapeutic cargo. This became possible due to the development of viral capsid modification method. Earlier in our laboratory and using phage display technology, phages to malignant breast cancer cells MDA-MB 231 were obtained. The goal of this study was the optimization of phage modification and the assessment of the effect of the latter on the efficiency of phage particle penetration into MDA-MB 231 cells. Methods: In this work, we used several methods, such as chemical phage modification using FAM-NHS ester, spectrophotometry, phage amplification, sequencing, phage titration, flow cytometry, and confocal microscopy. Results: We performed chemical phage modification using different concentrations of FAM-NHS dye (0.5 mM, 1 mM, 2 mM, 4 mM, 8 mM). It was shown that with an increase of the modification degree, the phage titer decreases. The maximum modification coefficient of the phage envelope with the FAM–NHS dye was observed with 4 mM modifying agent and had approximately 804,2 FAM molecules per phage. Through the immunofluorescence staining and flow cytometry methods, it was shown that the modified bacteriophage retains the ability to internalize into MDA-MB-231 cells. The estimation of the number of phages that could have penetrated into one tumor cell was conducted. Conclusions: Optimizing the conditions for phage modification can be an effective strategy for producing tumor-targeting diagnostic and therapeutic agents, i.e., theranostic drugs.

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“…Phages are highly specific and non-toxic, meaning that they exclusively infect bacteria and pose no threat to the cells of higher organisms [32]. Besides, when they act on the target pathogens, they do not damage the normal microflora of the host [33].…”

Section: Phages Infect Bacterial Biofilmsmentioning

confidence: 99%

Phages against Pathogenic Bacterial Biofilms and Biofilm-Based Infections: A Review

Liu

Zhang

et al. 2022

Pharmaceutics

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Bacterial biofilms formed by pathogens are known to be hundreds of times more resistant to antimicrobial agents than planktonic cells, making it extremely difficult to cure biofilm-based infections despite the use of antibiotics, which poses a serious threat to human health. Therefore, there is an urgent need to develop promising alternative antimicrobial therapies to reduce the burden of drug-resistant bacterial infections caused by biofilms. As natural enemies of bacteria, bacteriophages (phages) have the advantages of high specificity, safety and non-toxicity, and possess great potential in the defense and removal of pathogenic bacterial biofilms, which are considered to be alternatives to treat bacterial diseases. This work mainly reviews the composition, structure and formation process of bacterial biofilms, briefly discusses the interaction between phages and biofilms, and summarizes several strategies based on phages and their derivatives against biofilms and drug-resistant bacterial infections caused by biofilms, serving the purpose of developing novel, safe and effective treatment methods against biofilm-based infections and promoting the application of phages in maintaining human health.

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Bacteriophages as Therapeutic Preparations: What Restricts Their Application in Medicine

Cited by 15 publications

References 94 publications

RB49-like Bacteriophages Recognize O Antigens as One of the Alternative Primary Receptors

RB49-like Bacteriophages Recognize O Antigens as One of the Alternative Primary Receptors

Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications

Phages against Pathogenic Bacterial Biofilms and Biofilm-Based Infections: A Review

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