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Bacteriophage—Molecular Studies (6th Edition)
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Bacteriophage—Molecular Studies (6th Edition)

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

Deadline for manuscript submissions: 20 November 2025 | Viewed by 6101

Special Issue Editor

Prof. Dr. Alicja Wegrzyn

E-Mail Website
Guest Editor
Phage Therapy Center, University Center for Applied and Interdisciplinary Research, University of Gdansk, Gdansk, Poland
Interests: biology of bacteriophages; biodiversity of bacteriophages; regulation of bacteriophage development; regulation of phage gene expression; control of phage DNA replication; phage therapy; phages bearing genes of toxins; bacteriophage genomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bacteriophages, the viruses infecting bacterial cells, were first described 100 years ago, in 1915, by Frederick Twort. The scientist who introduced the name “bacteriophage” was Felix d’Herelle, who investigated these viruses for many years, leading to new fields of research, including bacteriophage therapy. In the following years, bacteriophages became important model organisms in molecular biology and genetics. Many basic discoveries were made during studies of these viruses, with such spectacular examples as demonstrating that DNA is a genetic material, viruses can encode enzymes, gene expression proceeds through mRNA molecules, the genetic code is based on nucleotide triplets, gene expression can be regulated by transcription antitermination, specific genes encode heat shock proteins, and specific mechanisms regulate DNA replication initiation based on the formation and rearrangements of protein–DNA complexes. The regulatory processes occurring in bacteriophage-infected cells have been considered paradigms of the control of developmental pathways. On the other hand, the history of research on bacteriophages also passed through dark times when, at the end of 20th century, there was the collective impression that we knew almost everything there was to know about these simple viruses, and that it was time to investigate more complex organisms instead. Nevertheless, subsequent discoveries have indicated that such an assumption was unequivocally false, and studies on the molecular biology and biotechnology of bacteriophages have once again become extensive. The interest in these viruses has increased dramatically, and it appears that we are far from understanding the biology of the vast majority of bacteriophages.

This Special Issue of the International Journal of Molecular Sciences is devoted to publishing papers on studies of bacteriophages at the molecular level. Papers on phage biodiversity, regulation of processes occurring during phage development, as well as the practical use of bacteriophages—including biotechnology and phage therapy—are welcome, providing the studies deal with the molecular level and utilize molecular biology methods. I am hopeful of building a great collection of articles devoted to recent discoveries in the field of bacteriophage molecular biology. Therefore, I invite you to submit manuscripts to this Special Issue as an excellent forum to share your discoveries in this fascinating research field.

Prof. Dr. Alicja Wegrzyn
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 biodiversity
  • regulation of bacteriophage development
  • molecular processes in bacteriophages
  • bacteriophage-based biotechnology
  • phage therapy

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Published Papers (4 papers)

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Research

23 pages, 8415 KiB  
Article
Zeta CrAss-like Phages, a Separate Phage Family Using a Variety of Adaptive Mechanisms to Persist in Their Hosts
by Igor V. Babkin, Valeria A. Fedorets, Artem Y. Tikunov, Ivan K. Baykov, Elizaveta A. Panina and Nina V. Tikunova
Int. J. Mol. Sci. 2025, 26(16), 7694; https://doi.org/10.3390/ijms26167694 - 8 Aug 2025
Viewed by 185
Abstract
Bacteriophages of the order Crassvirales are highly abundant and near-universal members of the human gut microbiome worldwide. Zeta crAss-like phages comprise a separate group in the order Crassvirales, and their genomes exhibit greater variability than genomes of crAss-like phages from other families within [...] Read more.
Bacteriophages of the order Crassvirales are highly abundant and near-universal members of the human gut microbiome worldwide. Zeta crAss-like phages comprise a separate group in the order Crassvirales, and their genomes exhibit greater variability than genomes of crAss-like phages from other families within the order. Zeta crAss-like phages employ multiple adaptation mechanisms, ensuring their survival despite host defenses and environmental pressure. Some Zeta crAss-like phages use alternative genetic coding and exploit diversity-generating retroelements (DGRs). These features suggest complex evolutionary relationships with their bacterial hosts, sustaining parasitic coexistence. Mutations in tail fiber proteins introduced by DGR can contribute to their adaptation to changes in the host cell surface and even expand the range of their hosts. In addition, the exchange of DNA polymerases via recombination makes it possible to overcome the bacterial anti-phage protection directed at these enzymes. Zeta crAss-like phages continuously adapt due to genetic diversification, host interaction tweaks, and counter-defense innovations, driving an evolutionary arms race with hosts. Based on the genome characteristics of the Zeta crAss-like phages, we propose to separate them into the Echekviridae family (“эчәк”—“intestines” in Tatar) following the tradition of using the word “intestines” in different languages, suggested previously. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies (6th Edition))
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19 pages, 2475 KiB  
Article
Phage Host Range Expansion Through Directed Evolution on Highly Phage-Resistant Strains of Klebsiella pneumoniae
by Kevin A. Burke, Tracey L. Peters, Olga A. Kirillina, Caitlin D. Urick, Bertran D. Walton, Jordan T. Bird, Nino Mzhavia, Martin O. Georges, Paphavee Lertsethtakarn, Lillian A. Musila, Mikeljon P. Nikolich and Andrey A. Filippov
Int. J. Mol. Sci. 2025, 26(15), 7597; https://doi.org/10.3390/ijms26157597 - 6 Aug 2025
Viewed by 387
Abstract
Multidrug-resistant (MDR) strains of Klebsiella pneumoniae present an acute threat as they continue to disseminate globally. Phage therapy has shown promise as a powerful approach to combat MDR infections, but narrow phage host ranges make development of broad acting therapeutics more challenging. The [...] Read more.
Multidrug-resistant (MDR) strains of Klebsiella pneumoniae present an acute threat as they continue to disseminate globally. Phage therapy has shown promise as a powerful approach to combat MDR infections, but narrow phage host ranges make development of broad acting therapeutics more challenging. The goal of this effort was to use in vitro directed evolution (the “Appelmans protocol”) to isolate K. pneumoniae phages with broader host ranges for improved therapeutic cocktails. Five myophages in the genus Jiaodavirus (family Straboviridae) with complementary activity were mixed and passaged against a panel of 11 bacterial strains including a permissive host and phage-resistant clinical isolates. Following multiple rounds of training, we collected phage variants displaying altered specificity or expanded host ranges compared with parental phages when tested against a 100 strain diversity panel of K. pneumoniae. Some phage variants gained the ability to lyse previously phage-resistant strains but lost activity towards previously phage-susceptible strains, while several variants had expanded activity. Whole-genome sequencing identified mutations and recombination events impacting genes associated with host tropism including tail fiber genes that most likely underlie the observed changes in host ranges. Evolved phages with broader activity are promising candidates for improved K. pneumoniae therapeutic phage cocktails. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies (6th Edition))
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22 pages, 19307 KiB  
Article
Therapeutic and Diagnostic Potential of a Novel K1 Capsule Dependent Phage, JSSK01, and Its Depolymerase in Multidrug-Resistant Escherichia coli Infections
by Naveen Gattuboyena, Yu-Chuan Tsai and Ling-Chun Lin
Int. J. Mol. Sci. 2024, 25(23), 12497; https://doi.org/10.3390/ijms252312497 - 21 Nov 2024
Viewed by 1456
Abstract
Bacteriophages are viruses that have the potential to combat bacterial infections caused by antimicrobial-resistant bacterial strains. In this study, we investigated a novel lytic bacteriophage, vB_EcoS_JSSK01, isolated from sewage in Hualien, Taiwan, which effectively combats multidrug-resistant (MDR) Escherichia coli of the K1 capsular [...] Read more.
Bacteriophages are viruses that have the potential to combat bacterial infections caused by antimicrobial-resistant bacterial strains. In this study, we investigated a novel lytic bacteriophage, vB_EcoS_JSSK01, isolated from sewage in Hualien, Taiwan, which effectively combats multidrug-resistant (MDR) Escherichia coli of the K1 capsular type. K1 E. coli is a major cause of severe extraintestinal infections, such as neonatal meningitis and urinary tract infections. Phage JSSK01 was found to have a genome size of 44,509 base pairs, producing approximately 123 particles per infected cell in 35 min, and was highly stable across a range of temperatures and pH. JSSK01 infected 59.3% of the MDR strains tested, and its depolymerase (ORF40) specifically degraded the K1 capsule in these bacteria. In a zebrafish model, JSSK01 treatment after infection significantly improved survival, with survival in the treated group reaching 100%, while that in the untreated group dropped to 10% after three days. The functional activity of depolymerase was validated using zone inhibition and agglutination tests. These results indicate that JSSK01 and its substrate-specific depolymerase have promising therapeutic and diagnostic applications against K1-encapsulated MDR E. coli infections. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies (6th Edition))
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42 pages, 122020 KiB  
Article
Origin, Evolution and Diversity of φ29-like Phages—Review and Bioinformatic Analysis
by Peter Evseev, Daria Gutnik, Alena Evpak, Anastasia Kasimova and Konstantin Miroshnikov
Int. J. Mol. Sci. 2024, 25(19), 10838; https://doi.org/10.3390/ijms251910838 - 9 Oct 2024
Cited by 2 | Viewed by 3236
Abstract
Phage φ29 and related bacteriophages are currently the smallest known tailed viruses infecting various representatives of both Gram-positive and Gram-negative bacteria. They are characterised by genomic content features and distinctive properties that are unique among known tailed phages; their characteristics include protein primer-driven [...] Read more.
Phage φ29 and related bacteriophages are currently the smallest known tailed viruses infecting various representatives of both Gram-positive and Gram-negative bacteria. They are characterised by genomic content features and distinctive properties that are unique among known tailed phages; their characteristics include protein primer-driven replication and a packaging process characteristic of this group. Searches conducted using public genomic databases revealed in excess of 2000 entries, including bacteriophages, phage plasmids and sequences identified as being archaeal that share the characteristic features of phage φ29. An analysis of predicted proteins, however, indicated that the metagenomic sequences attributed as archaeal appear to be misclassified and belong to bacteriophages. An analysis of the translated polypeptides of major capsid proteins (MCPs) of φ29-related phages indicated the dissimilarity of MCP sequences to those of almost all other known Caudoviricetes groups and a possible distant relationship to MCPs of T7-like (Autographiviridae) phages. Sequence searches conducted using HMM revealed the relatedness between the main structural proteins of φ29-like phages and an unusual lactococcal phage, KSY1 (Chopinvirus KSY1), whose genome contains two genes of RNA polymerase that are similar to the RNA polymerases of phages of the Autographiviridae and Schitoviridae (N4-like) families. An analysis of the tail tube proteins of φ29-like phages indicated their dissimilarity of the lower collar protein to tail proteins of all other viral groups, but revealed its possible distant relatedness with proteins of toxin translocation complexes. The combination of the unique features and distinctive origin of φ29-related phages suggests the categorisation of this vast group in a new order or as a new taxon of a higher rank. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies (6th Edition))
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