Phage-Bacteria Interplay in Health and Disease, Second Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Bacterial Viruses".

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 13562

Special Issue Editors


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Guest Editor
Department of Pathogen Biology and Immunology, University of Wroclaw, Wroclaw, Poland
Interests: microbiology; phage-bacteria interaction

E-Mail Website
Guest Editor
Department of Pathogen Biology and Immunology, Faculty of Biological Sciences, University of Wroclaw, Wroclaw, Poland
Interests: host–pathogen interplay; outer membrane vesicles; innate immunity; inflammation; cross-reactive antibodies; Moraxella catarrhalis
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Special Issue Information

Dear Colleagues,

Bacteriophages are obligatory parasites propagating in bacterial hosts in a lytic or lysogenic cycle. Phages are the most abundant biological particles in the world, responsible for: (i) dissolved and particulate organic matter circulation via host cell lysis; (ii) the regulation and biodiversity of populations by reducing the number of dominating bacteria; (iii) horizontal gene transfer (HGT) via transduction, or indirectly via the transformation of bacterial DNA released during cell lysis; and, finally, (iv) lysogenic conversion via temperate phages. Therefore, phages greatly affect microbial diversification as an integral part of each ecological niche, including the human body. The tremendous dynamics of phage–host interactions results in the continuous flow of genetic material, which drives the co-evolution of both entities.

In this Special Issue, we are looking for reports and reviews on the most current findings on phage’s role in the microbiome in health and disease. We welcome the submission of original studies, reviews, and mini-reviews covering, but not limited to, the following topics:

  • How phages affect the regulation and functioning of human/mammal microbial ecosystems as the consequence of specific and non-specific virus–bacteria interactions, including the shaping of microbial communities, the behavior and virulence of bacteria, as well as advantages versus drawbacks of phage-induced alterations;
  • How the mechanisms of bacterial defense against phages can drive the outcome of the disease/infection, including (i) active defense (receptor modification, CRISPR/Cas, R-M system, etc.), (ii) passive defense (OMVs release, secondary metabolites release, etc.), and (iii) the susceptibility of phage mutants/altered bacteria to host immune responses;
  • Bacteriophages as human immune modulators of innate and adaptive immunity, as well as human viral pathogens.

Dr. Grażyna Majkowska-Skrobek
Dr. Daria Augustyniak
Guest Editors

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Keywords

  • phage-bacteria interaction
  • phage-host interaction
  • phage resistance
  • microbiota and phagobiota interactions
  • immune response to phage presence
  • phage–bacteria co-evolution
  • phage–bacteria infection networks

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Published Papers (9 papers)

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Research

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23 pages, 7595 KiB  
Article
New Bacteriophage Pseudomonas Phage Ka2 from a Tributary Stream of Lake Baikal
by Valeriya Ilyina, Alina Gatina, Elena Trizna, Maria Siniagina, Liudmila Yadykova, Anastasiya Ivannikova, Georgiy Ozhegov, Daria Zhuravleva, Marina Fedorova, Anna Gorshkova, Peter Evseev, Valentin Drucker, Mikhail Bogachev, Shamil Validov, Maya Kharitonova and Airat Kayumov
Viruses 2025, 17(2), 189; https://doi.org/10.3390/v17020189 - 29 Jan 2025
Viewed by 962
Abstract
Pseudomonas aeruginosa, an opportunistic pathogen, causes various biofilm-associated infections like pneumonia, infections in cystic fibrosis patients, and urinary tract and burn infections with high morbidity and mortality, as well as low treatment efficacy due to the extremely wide spread of isolates with [...] Read more.
Pseudomonas aeruginosa, an opportunistic pathogen, causes various biofilm-associated infections like pneumonia, infections in cystic fibrosis patients, and urinary tract and burn infections with high morbidity and mortality, as well as low treatment efficacy due to the extremely wide spread of isolates with multidrug resistance. Here, we report the new bacteriophage Pseudomonas phage Ka2 isolated from a tributary stream of Lake Baikal and belonging to the Pbunavirus genus. Transmission electron microscopy resolved that Pseudomonas phage Ka2 has a capsid of 57 ± 9 nm and a contractile and inflexible tail of 115 ± 10 nm in the non-contracted state. The genome consists of 66,310 bp with a GC content of 55% and contains 96 coding sequences. Among them, 52 encode proteins have known functions, and none of them are potentially associated with lysogeny. The bacteriophage lyses 21 of 30 P. aeruginosa clinical isolates and decreases the MIC of amikacin, gentamicin, and cefepime up to 16-fold and the MIC of colistin up to 32-fold. When treating the biofilms with Ka2, the biomass was reduced by twice, and up to a 32-fold decrease in the antibiotics MBC against biofilm-embedded cells was achieved by the combination of Ka2 with cefepime for the PAO1 strain, along with a decrease of up to 16-fold with either amikacin or colistin for clinical isolates. Taken together, these data characterize the new Pseudomonas phage Ka2 as a promising tool for the combined treatment of infections associated with P. aeruginosa biofilms. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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11 pages, 1215 KiB  
Article
Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type Acinetobacter baumannii in Mouse Sepsis and Burn Skin Infection Models
by Alexander I. Borzilov, Nikolay V. Volozhantsev, Olga V. Korobova, Lyubov V. Kolupaeva, Evgenia S. Pereskokova, Tatiana I. Kombarova, Mikhail M. Shneider, Konstantin A. Miroshnikov, Ivan A. Dyatlov and Anastasia V. Popova
Viruses 2025, 17(1), 70; https://doi.org/10.3390/v17010070 - 6 Jan 2025
Viewed by 915
Abstract
Acinetobacter baumannii is a widely distributed nosocomial pathogen that causes various acute and chronic infections, particularly in immunocompromised patients. In this study, the activities of the K9-specific virulent phage AM24 and phage-encoded depolymerase DepAPK09 were assessed using in vivo mouse sepsis and burn [...] Read more.
Acinetobacter baumannii is a widely distributed nosocomial pathogen that causes various acute and chronic infections, particularly in immunocompromised patients. In this study, the activities of the K9-specific virulent phage AM24 and phage-encoded depolymerase DepAPK09 were assessed using in vivo mouse sepsis and burn skin infection models. In the mouse sepsis model, in the case of prevention or early treatment, a single K9-specific phage or recombinant depolymerase injection was able to protect 100% of the mice after parenteral infection with a lethal dose of A. baumannii of the K9-type, with complete eradication of the pathogen. In the case of delayed treatment, mouse survival decreased to 70% when injected with the phage and to 40% when treated with the recombinant enzyme. In the mouse burn skin infection model, the number of A. baumannii cells on the surface of the wound and in the deep layers of the skin decreased by several-fold after treatment with both the K9-specific phage and the recombinant depolymerase. The phage and recombinant depolymerase were highly stable and retained activity under a wide range of temperatures and pH values. The results obtained contribute to expanding our understanding of the in vivo therapeutic potential of specific phages and phage-derived depolymerases interacting with A. baumannii of different capsular types. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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19 pages, 8008 KiB  
Article
Genome Analysis of Anti-Phage Defense Systems and Defense Islands in Stenotrophomonas maltophilia: Preservation and Variability
by Ghadeer Jdeed, Vera V. Morozova and Nina V. Tikunova
Viruses 2024, 16(12), 1903; https://doi.org/10.3390/v16121903 - 10 Dec 2024
Viewed by 1629
Abstract
Anti-phage defense systems are widespread in bacteria due to the latter continuous adaptation to infection by bacteriophages (phages). Stenotrophomonas maltophilia has a high degree of intrinsic antibiotic resistance, which makes phage therapy relevant for the treatment of infections caused by this species. Studying [...] Read more.
Anti-phage defense systems are widespread in bacteria due to the latter continuous adaptation to infection by bacteriophages (phages). Stenotrophomonas maltophilia has a high degree of intrinsic antibiotic resistance, which makes phage therapy relevant for the treatment of infections caused by this species. Studying the array of anti-phage defense systems that could be found in S. maltophilia helps in better adapting the phages to the systems present in the pathogenic bacteria. Pangenome analysis of the available S. maltophilia strains with complete genomes that were downloaded from GenBank, including five local genomes, indicated a wide set of 72 defense systems and subsystems that varied between the strains. Seven of these systems were present in more than 20% of the studied genomes and the proteins encoded by the systems were variable in most of the cases. A total of 27 defense islands were revealed where defense systems were found; however, more than 60% of the instances of systems were found in four defense islands. Several elements linked to the transfer of these systems were found. No obvious associations between the pattern of distribution of the anti-phage defense systems of S. maltophilia and the phylogenetic features or the isolation site were found. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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13 pages, 1160 KiB  
Article
Assessment of Bacteriophage Pharmacokinetic Parameters After Intra-Articular Delivery in a Rat Prosthetic Joint Infection Model
by Jason Young, Mohammad Javad Shariyate, Prateek Misra, Shubham Laiwala, Ara Nazarian and Edward Kenneth Rodriguez
Viruses 2024, 16(11), 1800; https://doi.org/10.3390/v16111800 - 20 Nov 2024
Viewed by 994
Abstract
Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a Staphylococcus epidermidis [...] Read more.
Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a Staphylococcus epidermidis Kirschner wire-based prosthesis rat model. We used 52 male Sprague–Dawley rats in four groups: negative controls (no phage, sterile implant), PJI controls (bacteria, no phage), sterile phage (phages given, sterile implant), and PJI (bacteria, phages given). The PJI groups were inoculated with ~106 CFU of S. epidermidis. The groups receiving phage were intra-articularly injected with ~108 PFU of vB_SepM_Alex five days post-implantation. The rats were euthanized between 30 min and 48 h post-injection. The measured phage concentrations between the PJI rats and the sterile controls in periarticular tissues were not significantly different. In a noncompartmental pharmacokinetic analysis, the estimated phage half-lives were under 6 h (combined: 3.73 [IQR, 1.45, 10.07]). The maximum phage concentrations were reached within 2 h after administration (combined: 0.75 [0.50, 1.75]). The estimated phage mean residence time was approximately three hours (combined: 3.04 [1.44, 4.19]). Our study provides a preliminary set of pharmacokinetic parameters that can inform future phage dosing studies and animal models of phage therapy for PJIs. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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32 pages, 4747 KiB  
Article
Phage-Mediated Digestive Decolonization in a Gut-On-A-Chip Model: A Tale of Gut-Specific Bacterial Prosperity
by Brieuc Van Nieuwenhuyse, Maya Merabishvili, Nathalie Goeders, Kevin Vanneste, Bert Bogaerts, Mathieu de Jode, Joachim Ravau, Jeroen Wagemans, Leïla Belkhir and Dimitri Van der Linden
Viruses 2024, 16(7), 1047; https://doi.org/10.3390/v16071047 - 28 Jun 2024
Viewed by 1680
Abstract
Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has [...] Read more.
Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has been postulated as a promising preventive intervention. However, previous attempts at such eradication using oral antibiotics or probiotics have led to discouraging results. Phage therapy, the therapeutic use of bacteriophage viruses, might represent a worthy alternative in this context. Taking inspiration from this clinical challenge, we built Gut-On-A-Chip (GOAC) models, which are tridimensional cell culture models mimicking a simplified gut section. These were used to better understand bacterial dynamics under phage pressure using two relevant species: Pseudomonas aeruginosa and Escherichia coli. Model mucus secretion was documented by ELISA assays. Bacterial dynamics assays were performed in GOAC triplicates monitored for 72 h under numerous conditions, such as pre-, per-, or post-bacterial timing of phage introduction, punctual versus continuous phage administration, and phage expression of mucus-binding properties. The potential genomic basis of bacterial phage resistance acquired in the model was investigated by variant sequencing. The bacterial “escape growth” rates under phage pressure were compared to static in vitro conditions. Our results suggest that there is specific bacterial prosperity in this model compared to other in vitro conditions. In E. coli assays, the introduction of a phage harboring unique mucus-binding properties could not shift this balance of power, contradicting previous findings in an in vivo mouse model and highlighting the key differences between these models. Genomic modifications were correlated with bacterial phage resistance acquisition in some but not all instances, suggesting that alternate ways are needed to evade phage predation, which warrants further investigation. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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14 pages, 2008 KiB  
Article
Combinations of Bacteriophage Are Efficacious against Multidrug-Resistant Pseudomonas aeruginosa and Enhance Sensitivity to Carbapenem Antibiotics
by Christopher J. Kovacs, Erika M. Rapp, William R. Rankin, Sophia M. McKenzie, Brianna K. Brasko, Katherine E. Hebert, Beth A. Bachert, Andrew R. Kick, F. John Burpo and Jason C. Barnhill
Viruses 2024, 16(7), 1000; https://doi.org/10.3390/v16071000 - 21 Jun 2024
Cited by 3 | Viewed by 2451
Abstract
The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy [...] Read more.
The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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10 pages, 1191 KiB  
Article
Phage–Bacterial Interaction Alters Phenotypes Associated with Virulence in Acinetobacter baumannii
by Greater Kayode Oyejobi, Xiaoxu Zhang, Dongyan Xiong, Heng Xue, Mengjuan Shi, Hang Yang and Hongping Wei
Viruses 2024, 16(5), 743; https://doi.org/10.3390/v16050743 - 8 May 2024
Cited by 1 | Viewed by 1730
Abstract
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to [...] Read more.
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to assess the costs of phage resistance on the in vitro virulence of priority 1 nosocomial pathogenic bacterium, Acinetobacter baumannii. By subjecting phage-resistant variant Ev5-WHG of A. baumannii WHG40004 to several in vitro virulence profiles, we found that its resistance to phage is associated with reduced fitness in host microenvironments. Also, the mutant exhibited impaired adhesion and invasion to mammalian cells, as well as increased susceptibility to macrophage phagocytosis. Furthermore, the whole-genome sequencing of the mutant revealed that there exist multiple mutations which may play a role in phage resistance and altered virulence. Altogether, this study demonstrates that resistance to phage can significantly alter phenotypes associated with virulence in Acinetobacter baumannii. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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Review

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23 pages, 5085 KiB  
Review
Factors Affecting Phage–Bacteria Coevolution Dynamics
by Ghadeer Jdeed, Bogdana Kravchuk and Nina V. Tikunova
Viruses 2025, 17(2), 235; https://doi.org/10.3390/v17020235 - 8 Feb 2025
Viewed by 1050
Abstract
Bacteriophages (phages) have coevolved with their bacterial hosts for billions of years. With the rise of antibiotic resistance, the significance of using phages in therapy is increasing. Investigating the dynamics of phage evolution can provide valuable insights for pre-adapting phages to more challenging [...] Read more.
Bacteriophages (phages) have coevolved with their bacterial hosts for billions of years. With the rise of antibiotic resistance, the significance of using phages in therapy is increasing. Investigating the dynamics of phage evolution can provide valuable insights for pre-adapting phages to more challenging clones of their hosts that may arise during treatment. Two primary models describe interactions in phage–bacteria systems: arms race dynamics and fluctuating selection dynamics. Numerous factors influence which dynamics dominate the interactions between a phage and its host. These dynamics, in turn, affect the coexistence of phages and bacteria, ultimately determining which organism will adapt more effectively to the other, and whether a stable state will be reached. In this review, we summarize key findings from research on phage–bacteria coevolution, focusing on the different concepts that can describe these interactions, the factors that may contribute to the prevalence of one model over others, and the effects of various dynamics on both phages and bacteria. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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16 pages, 1078 KiB  
Review
Selected Mechanisms of Action of Bacteriophages in Bacterial Infections in Animals
by Renata Urban-Chmiel and Ewelina Pyzik
Viruses 2025, 17(1), 101; https://doi.org/10.3390/v17010101 - 14 Jan 2025
Viewed by 1319
Abstract
Bacteriophages, as ubiquitous bacterial viruses in various natural ecosystems, play an important role in maintaining the homeostasis of the natural microbiota. For many years, bacteriophages were not believed to act on eukaryotic cells; however, recent studies have confirmed their ability to affect eukaryotic [...] Read more.
Bacteriophages, as ubiquitous bacterial viruses in various natural ecosystems, play an important role in maintaining the homeostasis of the natural microbiota. For many years, bacteriophages were not believed to act on eukaryotic cells; however, recent studies have confirmed their ability to affect eukaryotic cells and interact with the host immune system. Due to their complex protein structure, phages can also directly or indirectly modulate immune processes, including innate immunity, by modulating phagocytosis and cytokine reactions, as well as acquired immunity, by producing antibodies and activating effector cells. They can therefore have a profound impact on the course of bacterial infections by stimulating and at the same time inhibiting the systemic pro-inflammatory response. This review article presents a characterization of the processes by which bacteriophages affect selected immune mechanisms in selected animal species. The results of our own experiments using calves are also presented as examples. The paper contains many new examples of potential uses of bacteriophages and their effects on eukaryotic cells, especially in the course of bacterial infections, which are extremely important in experimental treatments exploiting phages as alternatives to antibiotics. The positive results of the effects of bacteriophages on eukaryotic cells during infections open up promising new prospects for their use as natural tools in the treatment of bacterial, fungal, and viral diseases in animals and humans. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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