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Special Issue "Bacteriophage: Molecular Ecology and Pharmacology"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 25 April 2024 | Viewed by 5412

Special Issue Editor

Federal Research Center “Fundamentals of Biotechnology” of Russian Academy of Sciences, Leninsky Prospect, 33, Build. 2, 119071 Moscow, Russia
Interests: bacteriophage; phage-host interactions; phage ecology; phage therapy; molecular microbiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The discovery of bacterial viruses (bacteriophages) in 1915 and 1917 by Frederick Twort and Felix d’Herelle respectively, resulted from the research projects that shared in modern terms both ecological and applied goals. During the decades of research that followed this seminal discovery, the attention of phage research shifted to general biology of phages though the applied aspect also remained. The ecological perspective almost vanished and returned to the stage only at the very end of XX century.

Nowadays it became clear that bacteriophages are one of the major forces that moves and shapes the fascinating landscape of microbial world and its interactions with the rest of the Biosphere population. Phages influence almost any known aspect of bacterial biology and adopt immense variety of strategies to exert their ‘hidden power’, ranging from direct killing of the bacterial cells to protecting the host populations by actively subverting the immune reactions of macroorganisms. At the same time the growing world-wide crisis caused by the rapid spread of multidrug resistant bacterial pathogens greatly revived the interest of the scientific community to bacteriophage-mediated biocontrol technologies, at the first place to phage therapy but also to phage applications in agriculture, food industry and other fields aiming to reduce the use of antibiotics outside of medical facilities.

Thus, the need for the convergence of ecological and applied approaches in bacteriophage biology directly streams from the contemporary concepts in this field. The outcome of phage therapy or phage biocontrol interventions is always a result of ecological interactions between bacteria, viruses and environment (including that of human or animal body). And the possibilities and limitations of these technologies are largely defined by molecular mechanisms of phage-host and/or phage-macroorganisms interactions.

To this special issue we are aiming to attract high-level research and review papers concerning molecular aspects of bacteriophage ecology in the broad sense of the latter term. This will include the papers on bacteriophage genomics and metagenomics in free-living or symbiotic microbial systems, mechanisms of bacteriophage host range determination, influence of bacterial physiology on interactions with viruses and other ecologically relevant research topics. The papers regarding direct phage interactions with macroorganisms, including phage pharmacokinetics issues are specially welcome.

Prof. Dr. Andrey Letarov
Guest Editor

Manuscript Submission Information

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Keywords

  • bacteriophage ecology
  • bacteriophage pharmacology
  • intercell communication of bacteria
  • phage-host interactions
  • phage-host recognition
  • phage receptors
  • phage therapy

Published Papers (6 papers)

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Research

15 pages, 5514 KiB  
Article
Characterization of a Vibriophage Infecting Pathogenic Vibrio harveyi
Int. J. Mol. Sci. 2023, 24(22), 16202; https://doi.org/10.3390/ijms242216202 - 11 Nov 2023
Viewed by 448
Abstract
Bacterial diseases caused by Vibrio spp. are prevalent in aquaculture and can lead to high mortality rates among aquatic species and significant economic losses. With the increasing emergence of multidrug-resistant Vibrio strains, phage therapy is being explored as a potential alternative to antibiotics [...] Read more.
Bacterial diseases caused by Vibrio spp. are prevalent in aquaculture and can lead to high mortality rates among aquatic species and significant economic losses. With the increasing emergence of multidrug-resistant Vibrio strains, phage therapy is being explored as a potential alternative to antibiotics for biocontrol of infectious diseases. Here, a new lytic phage named vB_VhaS_R21Y (R21Y) was isolated against Vibrio harveyi BVH1 obtained from seawater from a scallop-farming area in Rongcheng, China. Its morphology, infection cycle, lytic profile, phage stability, and genetic features were characterized. Transmission electronic microscopy indicated that R21Y is siphovirus-like, comprising an icosahedral head (diameter 73.31 ± 2.09 nm) and long noncontractile tail (205.55 ± 0.75 nm). In a one-step growth experiment, R21Y had a 40-min latent period and a burst size of 35 phage particles per infected cell. R21Y was highly species-specific in the host range test and was relatively stable at pH 4–10 and 4–55 °C. Genomic analysis showed that R21Y is a double-stranded DNA virus with a genome size of 82,795 bp and GC content of 47.48%. Its high tolerance and lytic activity indicated that R21Y may be a candidate for phage therapy in controlling vibriosis in aquacultural systems. Full article
(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)
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18 pages, 5575 KiB  
Article
Genomes of a Novel Group of Phages That Use Alternative Genetic Code Found in Human Gut Viromes
Int. J. Mol. Sci. 2023, 24(20), 15302; https://doi.org/10.3390/ijms242015302 - 18 Oct 2023
Viewed by 486
Abstract
Metagenomics provides detection of phage genome sequences in various microbial communities. However, the use of alternative genetic codes by some phages precludes the correct analysis of their genomes. In this study, the unusual phage genome (phAss-1, 135,976 bp) was found after the de [...] Read more.
Metagenomics provides detection of phage genome sequences in various microbial communities. However, the use of alternative genetic codes by some phages precludes the correct analysis of their genomes. In this study, the unusual phage genome (phAss-1, 135,976 bp) was found after the de novo assembly of the human gut virome. Genome analysis revealed the presence of the TAG stop codons in 41 ORFs, including characteristic phage ORFs, and three genes of suppressor tRNA. Comparative analysis indicated that no phages with similar genomes were described. However, two phage genomes (BK046881_ctckW2 and BK025033_ct6IQ4) with substantial similarity to phAss-1 were extracted from the human gut metagenome data. These two complete genomes demonstrated 82.7% and 86.4% of nucleotide identity, respectively, similar genome synteny to phAss-1, the presence of suppressor tRNA genes and suppressor TAG stop codons in many characteristic phage ORFs. These data indicated that phAss-1, BK046881_ctckW2, and BK025033_ct6IQ4 are distinct species within the proposed Phassvirus genus. Moreover, a monophyletic group of divergent phage genomes containing the proposed Phassvirus genus was found among metagenome data. Several phage genomes from the group also contain ORFs with suppressor TAG stop codons, indicating the need to use various translation tables when depositing phage genomes in GenBank. Full article
(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)
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20 pages, 3238 KiB  
Article
Modulation of Caecal Microbiota and Metabolome Profile in Salmonella-Infected Broilers by Phage Therapy
Int. J. Mol. Sci. 2023, 24(20), 15201; https://doi.org/10.3390/ijms242015201 - 15 Oct 2023
Viewed by 1060
Abstract
Bacteriophage therapy is considered one of the most promising tools to control zoonotic bacteria, such as Salmonella, in broiler production. Phages exhibit high specificity for their targeted bacterial hosts, causing minimal disruption to the niche microbiota. However, data on the gut environment’s [...] Read more.
Bacteriophage therapy is considered one of the most promising tools to control zoonotic bacteria, such as Salmonella, in broiler production. Phages exhibit high specificity for their targeted bacterial hosts, causing minimal disruption to the niche microbiota. However, data on the gut environment’s response to phage therapy in poultry are limited. This study investigated the influence of Salmonella phage on host physiology through caecal microbiota and metabolome modulation using high-throughput 16S rRNA gene sequencing and an untargeted metabolomics approach. We employed 24 caecum content samples and 24 blood serum samples from 4-, 5- and 6-week-old broilers from a previous study where Salmonella phages were administered via feed in Salmonella-infected broilers, which were individually weighed weekly. Phage therapy did not affect the alpha or beta diversity of the microbiota. Specifically, we observed changes in the relative abundance of 14 out of the 110 genera using the PLS-DA and Bayes approaches. On the other hand, we noted changes in the caecal metabolites (63 up-accumulated and 37 down-accumulated out of the 1113 caecal metabolites). Nevertheless, the minimal changes in blood serum suggest a non-significant physiological response. The application of Salmonella phages under production conditions modulates the caecal microbiome and metabolome profiles in broilers without impacting the host physiology in terms of growth performance. Full article
(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)
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10 pages, 1575 KiB  
Article
IRAK3 Knockout and Wildtype THP-1 Monocytes as Models for Endotoxin Detection Assays and Fusobacterium nucleatum Bacteriophage FNU1 Cytokine Induction
Int. J. Mol. Sci. 2023, 24(20), 15108; https://doi.org/10.3390/ijms242015108 - 12 Oct 2023
Viewed by 470
Abstract
Microbial resistance to antibiotics poses a tremendous challenge. Bacteriophages may provide a useful alternative or adjunct to traditional antibiotics. To be used in therapy, bacteriophages need to be purified from endotoxins and tested for their effects on human immune cells. Interleukin-1 Receptor Associated [...] Read more.
Microbial resistance to antibiotics poses a tremendous challenge. Bacteriophages may provide a useful alternative or adjunct to traditional antibiotics. To be used in therapy, bacteriophages need to be purified from endotoxins and tested for their effects on human immune cells. Interleukin-1 Receptor Associated Kinase-3 (IRAK3) is a negative regulator of inflammation and may play a role in the modulation of immune signalling upon bacteriophage exposure to immune cells. This study aimed to investigate the immune effects of crude and purified bacteriophage FNU1, a bacteriophage that targets the oral pathobiont Fusobacterium nucleatum, on wildtype and IRAK3 knockout THP-1 monocytic cell lines. The IRAK3 knockout cell line was also used to develop a novel endotoxin detection assay. Exposure to crude FNU1 increased the production of pro-inflammatory cytokines (Tumour necrosis factor – alpha (TNF-α) and Interleukin 6 (IL-6)) compared to purified FNU1 in wildtype and IRAK3 knockout THP-1 monocytes. In the IRAK3 knockout THP-1 cells, exposure to crude FNU1 induced a higher immune response than the wildtype monocytes, supporting the suggestion that the inhibitory protein IRAK3 regulates reactions to endotoxins and impurities in bacteriophage preparations. Finally, the novel endotoxin detection assay generated here provides a robust and accurate method for determining endotoxin concentrations. Full article
(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)
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25 pages, 6917 KiB  
Article
Friunavirus Phage-Encoded Depolymerases Specific to Different Capsular Types of Acinetobacter baumannii
Int. J. Mol. Sci. 2023, 24(10), 9100; https://doi.org/10.3390/ijms24109100 - 22 May 2023
Cited by 2 | Viewed by 1255
Abstract
Acinetobacter baumannii is a critical priority nosocomial pathogen that produces a variety of capsular polysaccharides (CPSs), the primary receptors for specific depolymerase-carrying phages. In this study, the tailspike depolymerases (TSDs) encoded in genomes of six novel Friunaviruses, APK09, APK14, APK16, APK86, APK127v, APK128, [...] Read more.
Acinetobacter baumannii is a critical priority nosocomial pathogen that produces a variety of capsular polysaccharides (CPSs), the primary receptors for specific depolymerase-carrying phages. In this study, the tailspike depolymerases (TSDs) encoded in genomes of six novel Friunaviruses, APK09, APK14, APK16, APK86, APK127v, APK128, and one previously described Friunavirus phage, APK37.1, were characterized. For all TSDs, the mechanism of specific cleavage of corresponding A. baumannii capsular polysaccharides (CPSs) was established. The structures of oligosaccharide fragments derived from K9, K14, K16, K37/K3-v1, K86, K127, and K128 CPSs degradation by the recombinant depolymerases have been determined. The crystal structures of three of the studied TSDs were obtained. A significant reduction in mortality of Galleria mellonella larvae infected with A. baumannii of K9 capsular type was shown in the example of recombinant TSD APK09_gp48. The data obtained will provide a better understanding of the interaction of phage–bacterial host systems and will contribute to the formation of principles of rational usage of lytic phages and phage-derived enzymes as antibacterial agents. Full article
(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)
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13 pages, 512 KiB  
Article
Diversity-Generating Retroelements in Prokaryotic Immunity
Int. J. Mol. Sci. 2023, 24(6), 5614; https://doi.org/10.3390/ijms24065614 - 15 Mar 2023
Viewed by 1072
Abstract
Adaptive immunity systems found in different organisms fall into two major types. Prokaryotes possess CRISPR-Cas systems that recognize former invaders using memorized (captured) pieces of their DNA as pathogen signatures. Mammals possess a vast repertoire of antibodies and T-cell receptor variants generated in [...] Read more.
Adaptive immunity systems found in different organisms fall into two major types. Prokaryotes possess CRISPR-Cas systems that recognize former invaders using memorized (captured) pieces of their DNA as pathogen signatures. Mammals possess a vast repertoire of antibodies and T-cell receptor variants generated in advance. In this second type of adaptive immunity, a pathogen presentation to the immune system specifically activates the cells that express matching antibodies or receptors. These cells proliferate to fight the infection and form the immune memory. The principle of preemptive production of diverse defense proteins for future use can hypothetically take place in microbes too. We propose a hypothesis that prokaryotes employ diversity-generating retroelements to prepare defense proteins against yet-unknown invaders. In this study, we test this hypothesis with the methods of bioinformatics and identify several candidate defense systems based on diversity-generating retroelements. Full article
(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Diverse prophages of Salmonella enterica show potential role in disease and diversity
Author: Nale
Highlights: We examined 75 Salmonella genomes representing 15 important serovars. All strains harbour diverse prophages which encode abundant repertoire of virulence factors. Various close and distant genomic associations were formed among the prophages and those of other Enterobacteriaceae. Our data showed strong correlation between Salmonella prophages and numerous virulence factors and may contribute to diversity and pathogenicity of the serovars.

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