Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Bacteriophage: Molecular Ecology and Pharmacology

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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: closed (25 April 2024) | Viewed by 14695

Share This Special Issue

Special Issue Editor

Prof. Dr. Andrey Letarov

E-Mail Website
Guest 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

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

Published Papers (11 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

19 pages, 1028 KiB

Open AccessArticle

Correlation of Pseudomonas aeruginosa Phage Resistance with the Numbers and Types of Antiphage Systems

by Kevin A. Burke, Caitlin D. Urick, Nino Mzhavia, Mikeljon P. Nikolich and Andrey A. Filippov

Int. J. Mol. Sci. 2024, 25(3), 1424; https://doi.org/10.3390/ijms25031424 - 24 Jan 2024

Viewed by 1134

Abstract

Phage therapeutics offer a potentially powerful approach for combating multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using the web-server tool PADLOC (prokaryotic antiviral defense locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring resistance. Full article

(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)

► Show Figures

Figure 1

19 pages, 21947 KiB

Open AccessArticle

Tentaclins—A Novel Family of Phage Receptor-Binding Proteins That Can Be Hypermutated by DGR Systems

by Ivan K. Baykov, Artem Y. Tikunov, Igor V. Babkin, Valeria A. Fedorets, Elena V. Zhirakovskaia and Nina V. Tikunova

Int. J. Mol. Sci. 2023, 24(24), 17324; https://doi.org/10.3390/ijms242417324 - 10 Dec 2023

Viewed by 823

Abstract

Diversity-generating retroelements (DGRs) are prokaryotic systems providing rapid modification and adaptation of target proteins. In phages, the main targets of DGRs are receptor-binding proteins that are usually parts of tail structures and the variability of such host-recognizing structures enables phage adaptation to changes on the bacterial host surface. Sometimes, more than one target gene containing a hypermutated variable repeat (VR) can be found in phage DGRs. The role of mutagenesis of two functionally different genes is unclear. In this study, several phage genomes that contain DGRs with two target genes were found in the gut virome of healthy volunteers. Bioinformatics analysis of these genes indicated that they encode proteins with different topology; however, both proteins contain the C-type lectin (C-lec) domain with a hypermutated beta-hairpin on its surface. One of the target proteins belongs to a new family of proteins with a specific topology: N-terminal C-lec domain followed by one or more immunoglobulin domains. Proteins from the new family were named tentaclins after TENTACLe + proteIN. The genes encoding such proteins were found in the genomes of prophages and phages from the gut metagenomes. We hypothesized that tentaclins are involved in binding either to bacterial receptors or intestinal/immune cells. Full article

(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)

► Show Figures

Figure 1

15 pages, 7345 KiB

Open AccessArticle

How Do Phages Disrupt the Structure of Enterococcus faecalis Biofilm?

by Magdalena Moryl, Antoni Różalski, Jose Antonio Poli de Figueiredo and Aleksandra Palatyńska-Ulatowska

Int. J. Mol. Sci. 2023, 24(24), 17260; https://doi.org/10.3390/ijms242417260 - 08 Dec 2023

Cited by 1 | Viewed by 813

Abstract

Biofilms are composed of multicellular communities of microbial cells and their self-secreted extracellular polymeric substances (EPS). The viruses named bacteriophages can infect and lyze bacterial cells, leading to efficient biofilm eradication. The aim of this study was to analyze how bacteriophages disrupt the biofilm structure by killing bacterial cells and/or by damaging extracellular polysaccharides, proteins, and DNA. The use of colorimetric and spectrofluorimetric methods and confocal laser scanning microscopy (CLSM) enabled a comprehensive assessment of phage activity against E. faecalis biofilms. The impact of the phages vB_Efa29212_2e and vB_Efa29212_3e was investigated. They were applied separately or in combination on 1-day and 7-day-old biofilms. Phages 2e effectively inhibited the growth of planktonic cells with a limited effect on the biofilm. They did not notably affect extracellular polysaccharides and proteins; however, they increased DNA levels. Phages 3e demonstrated a potent and dispersing impact on E. faecalis biofilms, despite being slightly less effective than bacteriophages 2e against planktonic cells. Phages 3e reduced the amount of extracellular polysaccharides and increased eDNA levels in both 1-day-old and 7-day-old biofilm cultures. Phage cocktails had a strong antimicrobial effect on both planktonic and biofilm-associated bacteria. A significant reduction in the levels of polysaccharides, proteins, and eDNA in 1-day-old biofilm samples was noted, which confirms that phages interfere with the structure of E. faecalis biofilm by killing bacterial cells and affecting extracellular polymer levels. Full article

(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)

► Show Figures

Figure 1

15 pages, 5514 KiB

Open AccessArticle

Characterization of a Vibriophage Infecting Pathogenic Vibrio harveyi

by Yingying Li, Huayi Yun, Ruo Chen, Nianzhi Jiao, Qiang Zheng, Yunlan Yang and Rui Zhang

Int. J. Mol. Sci. 2023, 24(22), 16202; https://doi.org/10.3390/ijms242216202 - 11 Nov 2023

Viewed by 1061

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 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)

► Show Figures

Figure 1

18 pages, 5575 KiB

Open AccessArticle

Genomes of a Novel Group of Phages That Use Alternative Genetic Code Found in Human Gut Viromes

by Igor Babkin, Artem Tikunov, Vera Morozova, Andrey Matveev, Vitaliy V. Morozov and Nina Tikunova

Int. J. Mol. Sci. 2023, 24(20), 15302; https://doi.org/10.3390/ijms242015302 - 18 Oct 2023

Cited by 1 | Viewed by 844

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 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)

► Show Figures

Figure 1

20 pages, 3238 KiB

Open AccessArticle

Modulation of Caecal Microbiota and Metabolome Profile in Salmonella-Infected Broilers by Phage Therapy

by Laura Lorenzo-Rebenaque, Cristina Casto-Rebollo, Gianfranco Diretto, Sarah Frusciante, Juan Carlos Rodríguez, María-Paz Ventero, Carmen Molina-Pardines, Santiago Vega, Clara Marin and Francisco Marco-Jiménez

Int. J. Mol. Sci. 2023, 24(20), 15201; https://doi.org/10.3390/ijms242015201 - 15 Oct 2023

Cited by 1 | Viewed by 1573

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 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)

► Show Figures

Figure 1

10 pages, 1575 KiB

Open AccessArticle

IRAK3 Knockout and Wildtype THP-1 Monocytes as Models for Endotoxin Detection Assays and Fusobacterium nucleatum Bacteriophage FNU1 Cytokine Induction

by Siti Saleha Binte Mohamed Yakob Adil, Mwila Kabwe, Cassandra Cianciarulo, Trang Hong Nguyen, Helen Irving and Joseph Tucci

Int. J. Mol. Sci. 2023, 24(20), 15108; https://doi.org/10.3390/ijms242015108 - 12 Oct 2023

Viewed by 1096

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 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)

► Show Figures

Figure 1

25 pages, 6917 KiB

Open AccessArticle

Friunavirus Phage-Encoded Depolymerases Specific to Different Capsular Types of Acinetobacter baumannii

by Olga Y. Timoshina, Anastasia A. Kasimova, Mikhail M. Shneider, Ilya O. Matyuta, Alena Y. Nikolaeva, Peter V. Evseev, Nikolay P. Arbatsky, Alexander S. Shashkov, Alexander O. Chizhov, Andrey A. Shelenkov, Yulia V. Mikhaylova, Pavel V. Slukin, Nikolay V. Volozhantsev, Konstantin M. Boyko, Yuriy A. Knirel, Konstantin A. Miroshnikov and Anastasia V. Popova

Int. J. Mol. Sci. 2023, 24(10), 9100; https://doi.org/10.3390/ijms24109100 - 22 May 2023

Cited by 5 | Viewed by 1791

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, 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)

► Show Figures

Figure 1

13 pages, 512 KiB

Open AccessArticle

Diversity-Generating Retroelements in Prokaryotic Immunity

by Ilya S. Belalov, Arseniy A. Sokolov and Andrey V. Letarov

Int. J. Mol. Sci. 2023, 24(6), 5614; https://doi.org/10.3390/ijms24065614 - 15 Mar 2023

Cited by 1 | Viewed by 1551

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 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)

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 1729 KiB

Open AccessReview

Bacterial Virus Forcing of Bacterial O-Antigen Shields: Lessons from Coliphages

by Andrey V. Letarov

Int. J. Mol. Sci. 2023, 24(24), 17390; https://doi.org/10.3390/ijms242417390 - 12 Dec 2023

Cited by 1 | Viewed by 1276

Abstract

In most Gram-negative bacteria, outer membrane (OM) lipopolysaccharide (LPS) molecules carry long polysaccharide chains known as the O antigens or O polysaccharides (OPS). The OPS structure varies highly from strain to strain, with more than 188 O serotypes described in E. coli. Although many bacteriophages recognize OPS as their primary receptors, these molecules can also screen OM proteins and other OM surface receptors from direct interaction with phage receptor-binding proteins (RBP). In this review, I analyze the body of evidence indicating that most of the E. coli OPS types robustly shield cells completely, preventing phage access to the OM surface. This shield not only blocks virulent phages but also restricts the acquisition of prophages. The available data suggest that OPS-mediated OM shielding is not merely one of many mechanisms of bacterial resistance to phages. Rather, it is an omnipresent factor significantly affecting the ecology, phage–host co-evolution and other related processes in E. coli and probably in many other species of Gram-negative bacteria. The phages, in turn, evolved multiple mechanisms to break through the OPS layer. These mechanisms rely on the phage RBPs recognizing the OPS or on using alternative receptors exposed above the OPS layer. The data allow one to forward the interpretation that, regardless of the type of receptors used, primary receptor recognition is always followed by the generation of a mechanical force driving the phage tail through the OPS layer. This force may be created by molecular motors of enzymatically active tail spikes or by virion structural re-arrangements at the moment of infection. Full article

(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)

► Show Figures

Figure 1

23 pages, 1447 KiB

Open AccessReview

RNA and Single-Stranded DNA Phages: Unveiling the Promise from the Underexplored World of Viruses

by Huong Minh Nguyen, Shinya Watanabe, Sultana Sharmin, Tomofumi Kawaguchi, Xin-Ee Tan, Dhammika Leshan Wannigama and Longzhu Cui

Int. J. Mol. Sci. 2023, 24(23), 17029; https://doi.org/10.3390/ijms242317029 - 01 Dec 2023

Cited by 2 | Viewed by 1854

Abstract

RNA and single-stranded DNA (ssDNA) phages make up an understudied subset of bacteriophages that have been rapidly expanding in the last decade thanks to advancements in metaviromics. Since their discovery, applications of genetic engineering to ssDNA and RNA phages have revealed their immense potential for diverse applications in healthcare and biotechnology. In this review, we explore the past and present applications of this underexplored group of phages, particularly their current usage as therapeutic agents against multidrug-resistant bacteria. We also discuss engineering techniques such as recombinant expression, CRISPR/Cas-based genome editing, and synthetic rebooting of phage-like particles for their role in tailoring phages for disease treatment, imaging, biomaterial development, and delivery systems. Recent breakthroughs in RNA phage engineering techniques are especially highlighted. We conclude with a perspective on challenges and future prospects, emphasizing the untapped diversity of ssDNA and RNA phages and their potential to revolutionize biotechnology and medicine. Full article

(This article belongs to the Special Issue Bacteriophage: Molecular Ecology and Pharmacology)

► Show Figures

Journal Menu

Journal Browser

Bacteriophage: Molecular Ecology and Pharmacology

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI