-
International Journal of Molecular... Nov 2022Bacteriophages have long been considered only as infectious agents that affect bacterial hosts. However, recent studies provide compelling evidence that these viruses... (Review)
Review
Bacteriophages have long been considered only as infectious agents that affect bacterial hosts. However, recent studies provide compelling evidence that these viruses are able to successfully interact with eukaryotic cells at the levels of the binding, entry and expression of their own genes. Currently, bacteriophages are widely used in various areas of biotechnology and medicine, but the most intriguing of them is cancer therapy. There are increasing studies confirming the efficacy and safety of using phage-based vectors as a systemic delivery vehicle of therapeutic genes and drugs in cancer therapy. Engineered bacteriophages, as well as eukaryotic viruses, demonstrate a much greater efficiency of transgene delivery and expression in cancer cells compared to non-viral gene transfer methods. At the same time, phage-based vectors, in contrast to eukaryotic viruses-based vectors, have no natural tropism to mammalian cells and, as a result, provide more selective delivery of therapeutic cargos to target cells. Moreover, numerous data indicate the presence of more complex molecular mechanisms of interaction between bacteriophages and eukaryotic cells, the further study of which is necessary both for the development of gene therapy methods and for understanding the cancer nature. In this review, we summarize the key results of research into aspects of phage-eukaryotic cell interaction and, in particular, the use of phage-based vectors for highly selective and effective systemic cancer gene therapy.
Topics: Animals; Bacteriophages; Gene Transfer Techniques; Genetic Therapy; Pharmaceutical Preparations; Genes, Neoplasm; Mammals; Neoplasms
PubMed: 36430720
DOI: 10.3390/ijms232214245 -
FEMS Microbiology Reviews Feb 2022We are in the midst of a golden age of uncovering defense systems against bacteriophages. Apart from the fundamental interest in these defense systems, and revolutionary... (Review)
Review
We are in the midst of a golden age of uncovering defense systems against bacteriophages. Apart from the fundamental interest in these defense systems, and revolutionary applications that have been derived from them (e.g. CRISPR-Cas9 and restriction endonucleases), it is unknown how defense systems contribute to resistance formation against bacteriophages in clinical settings. Bacteriophages are now being reconsidered as therapeutic agents against bacterial infections due the emergence of multidrug resistance. However, bacteriophage resistance through defense systems and other means could hinder the development of successful phage-based therapies. Here, we review the current state of the field of bacteriophage defense, highlight the relevance of bacteriophage defense for potential clinical use of bacteriophages as therapeutic agents and suggest new directions of research.
Topics: Bacterial Infections; Bacteriophages; CRISPR-Cas Systems; Humans; Phage Therapy
PubMed: 34558600
DOI: 10.1093/femsre/fuab048 -
Archives of Virology Aug 2018High-throughput sequencing (HTS) and its use in recovering and assembling novel virus sequences from environmental, human clinical, veterinary and plant samples has... (Review)
Review
High-throughput sequencing (HTS) and its use in recovering and assembling novel virus sequences from environmental, human clinical, veterinary and plant samples has unearthed a vast new catalogue of viruses. Their classification, known by their sequences alone, sets a major challenge to traditional virus taxonomy, especially at the family and species levels, which have been historically based largely on descriptive taxon definitions. These typically entail some knowledge of their phenotypic properties, including replication strategies, virion structure and clinical and epidemiological features, such as host range, geographical distribution and disease outcomes. Little to no information on these attributes is available, however, for viruses identified in metagenomic datasets. If such viruses are to be included in virus taxonomy, their assignments will have to be guided largely or entirely by metrics of genetic relatedness. The immediate problem here is that the International Committee on Taxonomy of Viruses (ICTV), an organisation that authorises the taxonomic classification of viruses, provides little or no guidance on how similar or how divergent viruses must be in order to be considered members of new species or new families. We have recently developed a method for scoring genomic (dis)similarity between viruses (Genome Relationships Applied to Virus Taxonomy - GRAViTy) among the eukaryotic and prokaryotic viruses currently classified by the ICTV. At the family and genus levels, we found large-scale consistency between genetic relationships and their taxonomic assignments for eukaryotic viruses of all genome configurations and genome sizes. Family assignments of prokaryotic viruses have, however, been made at a quite different genetic level, and groupings currently classified as sub-families are a much better match to the eukaryotic virus family level. These findings support the ongoing reorganisation of bacteriophage taxonomy by the ICTV Phage Study Group. A rapid and objective means to explore metagenomic viral diversity and make evidence-based assignments for such viruses at each taxonomic layer is essential. Analysis of sequences by GRAViTy provides evidence that family (and genus) assignments of currently classified viruses are largely underpinned by genomic relatedness, and these features could serve as a guide towards an evidence-based classification of metagenomic viruses in the future.
Topics: Animals; Bacteriophages; Genome, Viral; Humans; Phylogeny; Virus Diseases; Viruses
PubMed: 30039318
DOI: 10.1007/s00705-018-3938-z -
Cell Host & Microbe Feb 2019The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable... (Review)
Review
The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >10 viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat. Before delving into their function, we need to first overcome the challenges associated with studying and characterizing the phageome. In this Review, we summarize the available methods and main findings regarding taxonomic composition, community structure, and population dynamics in the human gut phageome. We also discuss the main challenges in the field and identify promising avenues for future research.
Topics: Bacteria; Bacteriophages; Gastrointestinal Tract; Host-Parasite Interactions; Humans; Microbiota; Population Dynamics
PubMed: 30763534
DOI: 10.1016/j.chom.2019.01.017 -
Microbiological Research 2018Bacteriophage particles are the most abundant biological entities on our planet, infecting specific bacterial hosts in every known environment and being major drivers of... (Review)
Review
Bacteriophage particles are the most abundant biological entities on our planet, infecting specific bacterial hosts in every known environment and being major drivers of bacterial adaptive evolution. The study of bacteriophage particles potentially sheds light on the development of new biotechnology products. Bacteriophage therapy, although not new, makes use of strictly lytic phage particles as an alternative in the antimicrobial treatment of resistant bacterial infections and is being rediscovered as a safe method due to the fact that these biological entities devoid of any metabolic machinery do not have affinity to eukaryotic cells. Furthermore, bacteriophage-based vaccination is emerging as one of the most promising preventive strategies. This review paper discusses the biological nature of bacteriophage particles, their mode(s) of action and potential exploitation in modern biotechnology. Topics covered in detail include the potential of bacteriophage particles in human infections (bacteriophage therapy), nanocages for gene delivery, food biopreservation and safety, biocontrol of plant pathogens, phage display, bacterial biosensing devices, vaccines and vaccine carriers, biofilm and bacterial growth control, surface disinfection, corrosion control, together with structural and functional stabilization issues.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Biofilms; Biological Control Agents; Biosensing Techniques; Biotechnology; Corrosion; DNA Packaging; Dental Caries; Disinfection; Food Preservation; Food Safety; Gene Transfer Techniques; Humans; Nanostructures; Phage Therapy; Vaccination; Vaccines
PubMed: 29853167
DOI: 10.1016/j.micres.2018.04.007 -
Applied Microbiology and Biotechnology Mar 2016Bacteriophages (phages), natural enemies of bacteria, can encode enzymes able to degrade polymeric substances. These substances can be found in the bacterial cell... (Review)
Review
Bacteriophages (phages), natural enemies of bacteria, can encode enzymes able to degrade polymeric substances. These substances can be found in the bacterial cell surface, such as polysaccharides, or are produced by bacteria when they are living in biofilm communities, the most common bacterial lifestyle. Consequently, phages with depolymerase activity have a facilitated access to the host receptors, by degrading the capsular polysaccharides, and are believed to have a better performance against bacterial biofilms, since the degradation of extracellular polymeric substances by depolymerases might facilitate the access of phages to the cells within different biofilm layers. Since the diversity of phage depolymerases is not yet fully explored, this is the first review gathering information about all the depolymerases encoded by fully sequenced phages. Overall, in this study, 160 putative depolymerases, including sialidases, levanases, xylosidases, dextranases, hyaluronidases, peptidases as well as pectate/pectin lyases, were found in 143 phages (43 Myoviridae, 47 Siphoviridae, 37 Podoviridae, and 16 unclassified) infecting 24 genera of bacteria. We further provide information about the main applications of phage depolymerases, which can comprise areas as diverse as medical, chemical, or food-processing industry.
Topics: Bacteriophages; Biopolymers; Biotransformation; Hydrolases; Lyases
PubMed: 26767986
DOI: 10.1007/s00253-015-7247-0 -
Annual Review of Virology Sep 2021Bacteriophages-viruses that infect bacteria-are abundant within our bodies, but their significance to human health is only beginning to be explored. Here, we synthesize...
Bacteriophages-viruses that infect bacteria-are abundant within our bodies, but their significance to human health is only beginning to be explored. Here, we synthesize what is currently known about our phageome and its interactions with the immune system. We first review how phages indirectly affect immunity via bacterial expression of phage-encoded proteins. We next review how phages directly influence innate immunity and bacterial clearance. Finally, we discuss adaptive immunity against phages and its implications for phage/bacterial interactions. In light of these data, we propose that our microbiome can be understood as an interconnected network of bacteria, bacteriophages, and human cells and that the stability of these tri-kingdom interactions may be important for maintaining our immunologic and metabolic health. Conversely, the disruption of this balance, through exposure to exogenous phages, microbial dysbiosis, or immune dysregulation, may contribute to disease.
Topics: Bacteria; Bacteriophages; Humans; Immune System; Microbiota; Viruses
PubMed: 34014761
DOI: 10.1146/annurev-virology-091919-074551 -
Trends in Biotechnology May 2023In recent years, bacteriophage research has been boosted by a rising interest in using phage therapy to treat antibiotic-resistant bacterial infections. In addition,... (Review)
Review
In recent years, bacteriophage research has been boosted by a rising interest in using phage therapy to treat antibiotic-resistant bacterial infections. In addition, there is a desire to use phages and their unique proteins for specific biocontrol applications and diagnostics. However, the ability to manipulate phage genomes to understand and control gene functions, or alter phage properties such as host range, has remained challenging due to a lack of universal selectable markers. Here, we discuss the state-of-the-art techniques to engineer and select desired phage genomes using advances in cell-free methodologies and clustered regularly interspaced short palindromic repeats-CRISPR associated protein (CRISPR-Cas) counter-selection approaches.
Topics: Bacteriophages; CRISPR-Cas Systems; Genome, Viral; Bacteria
PubMed: 36117025
DOI: 10.1016/j.tibtech.2022.08.008 -
Polish Journal of Microbiology Feb 2022Bacteriophages are viruses infecting bacteria and propagating in bacterial cells. They were discovered over 100 years ago, and for decades they played crucial roles as... (Review)
Review
Bacteriophages are viruses infecting bacteria and propagating in bacterial cells. They were discovered over 100 years ago, and for decades they played crucial roles as models in genetics and molecular biology and as tools in genetic engineering and biotechnology. Now we also recognize their huge role in natural environment and their importance in human health and disease. Despite our understanding of bacteriophage mechanisms of development, these viruses are described as parasites or predators in the literature. From the biological point of view, there are fundamental differences between parasites and predators. Therefore, in this article, I asked whether bacteriophages should be classified as former or latter biological entities. Analysis of the literature and biological definitions led me to conclude that bacteriophages are parasites rather than predators and should be classified and described as such. If even more precise ecological classification is needed, bacteriophages can perhaps be included in the group of parasitoids. It might be the most appropriate formal classification of these viruses, especially if strictly virulent phages are considered, contrary to phages which lysogenize host cells and those which develop according to the permanent infection mode (or chronic cycle, like filamentous phages) revealing features of classical parasites.
Topics: Animals; Bacteria; Bacteriophages; Humans; Parasites
PubMed: 35635166
DOI: 10.33073/pjm-2022-005 -
European Review For Medical and... Dec 2021The aim of the study was to show the importance of developing techniques that could exploit the potential of bacteriophages as therapeutics or food supplements. (Review)
Review
OBJECTIVE
The aim of the study was to show the importance of developing techniques that could exploit the potential of bacteriophages as therapeutics or food supplements.
MATERIALS AND METHODS
PubMed database was searched using the following combination of keywords: (bacteriophage) AND (human therapy); (natural bacteriophage) AND (application).
RESULTS
The increasing antibiotic resistance of many bacterial strains is making standard antibiotic treatments less effective. Phage therapy provides a non-antibiotic alternative with greater specificity and without harmful effects on the human microbiota. Phages target their specific bacteria, replicate, and then, destroy the host pathogen. Bacteriophages may be administered by several routes, including topical, oral and intravenous. They not only destroy the host pathogen but, in some cases, increase the sensitivity of host bacteria to antibiotics. Various studies have shown that combining phage therapy and antibiotic treatment can be effective against bacterial infections. Clinical trials of phage therapy have shown promising results for various human diseases and conditions. With advances in genetic engineering and molecular techniques, bacteriophages will be able to target a wide range of bacteria.
CONCLUSIONS
In the future, phage therapy promises to become an effective therapeutic option for bacterial infections. Since many potentially beneficial bacteriophages can be found in food, supplements containing bacteriophages could be designed to remodel gut microbiota and eliminate pathogenic bacteria. Remodeling of gut microbiota could correct gut dysbiosis. The order of phages known to have these promising activities is Caudovirales, especially the families Siphoviridae and Myoviridae.
Topics: Bacterial Infections; Bacteriophages; Culture Techniques; Dysbiosis; Gastrointestinal Microbiome; Humans; Phage Therapy
PubMed: 34890040
DOI: 10.26355/eurrev_202112_27339